# "Kids Conquering Cancer: Flipping the hierarchy to find new diet-based interventions for EGFR and HPV-driven cancers"

March 09, 2022## Information

Yale Cancer Center Grand Rounds | March 8, 2022

Presentation by: Alana M. O'Reilly, PhD

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- 00:00My great pleasure to introduce our
- 00:02grand round speaker doctor Lana Riley.
- 00:04She's the 1st in water.
- 00:06Hope is going to be a long series
- 00:07of lecturers speaking on education,
- 00:09training and career development.
- 00:11This was actually Barbara Burtness idea,
- 00:13so Doctor Riley Hills to us from
- 00:14the Fox Chase Cancer Center where
- 00:16she's in associate professor in
- 00:18the Molecular therapeutics program.
- 00:19She's a scientific director of the
- 00:21immersion science program at Fox Chase,
- 00:23and she's also the executive
- 00:25director of the Eccles Institute,
- 00:28which is a hub where students,
- 00:29teachers and scientists.
- 00:30All joined forces to focus on
- 00:32critical biomedical problems,
- 00:34such as dietary effects on cancer.
- 00:37They're developing,
- 00:37cutting edge projects,
- 00:39and they enhancing scientific leadership
- 00:41within the community in Philadelphia.
- 00:43For for these efforts, Dr.
- 00:45Riley recently received the Elizabeth W.
- 00:47Jones Award for Excellence in Education
- 00:49from the Genetics Society of America.
- 00:51Among her many accolades,
- 00:53she received her pH D in cell and
- 00:55developmental biology at Harvard
- 00:56and a research interest involved
- 00:58nutritional mechanisms that influence
- 01:00stem cell function and development.
- 01:02She's the recipient of multiple NIH
- 01:04awards for her research on stem
- 01:07cells and epithelial homeostasis,
- 01:08and today she's going to be talking
- 01:10to us both about her outreach and
- 01:12education and her own research.
- 01:14In a talk that's entitled kids
- 01:16conquering cancer,
- 01:17flipping the hierarchy to find
- 01:19new diet based interventions for
- 01:21EGFR and HPV driven cancers.
- 01:23So, without further ado,
- 01:24it's my pleasure to turn the
- 01:26platform over to Doctor O'Reilly.
- 01:33It's really a pleasure to be here
- 01:34and thank you for inviting me.
- 01:36I'm also my very first research mentor.
- 01:40Anton Bennett is one of your faculty
- 01:43members and everything I know I
- 01:45learned from Anton and Venelles lab.
- 01:47So yeah, today I'm going to talk to
- 01:50you about mostly about our diet based
- 01:52programs involving high school students.
- 01:55So one of the things I want you all to start
- 01:58thinking about as we start here is why.
- 02:00Why did you enter science?
- 02:02A lot of times you know people ask
- 02:04us this question in all kinds of
- 02:07different applications and most of
- 02:09the answers are fairly similar.
- 02:11A little bit canned.
- 02:12I've loved science since childhood.
- 02:14I like to answer questions.
- 02:17I have some aspect of love love,
- 02:20love for science here or I care
- 02:23about somebody very much.
- 02:24So one of the things that we wanna
- 02:26do is to connect these puzzle pieces
- 02:28together to make an inclusive environment
- 02:30so that everyone can participate.
- 02:32So why do we even want inclusion?
- 02:34Why does it matter if we're all kind of
- 02:36similar people with similar ideas and
- 02:38we're going to work together better, right?
- 02:40But but that sort of limits our discoveries,
- 02:43right?
- 02:43So if we don't embrace.
- 02:45The life experiences and knowledge
- 02:47of all different types of people.
- 02:49Then we're essentially missing things
- 02:51that we could otherwise gather together.
- 02:54So why is inclusion so hard?
- 02:56Why is it so hard like we keep hearing
- 02:59about diversity, equity inclusion efforts,
- 03:02and failing and failing and failing?
- 03:05Why? Why is this so hard?
- 03:07So one of the really big problems we have,
- 03:10especially in a city like Philadelphia,
- 03:11which is 80% underrepresented
- 03:14minorities in science,
- 03:16is that we have a major attrition
- 03:19of scientists as they move up in
- 03:22the in the scientific pipeline.
- 03:24So in terms of bachelors degrees,
- 03:26it's still under representation,
- 03:27but this number plummets by
- 03:29the time you get to postdocs.
- 03:32And then there has been exactly
- 03:330 gains in full professors for
- 03:36underrepresented minorities.
- 03:38In many decades. So what's the deal?
- 03:41Why is this happening?
- 03:42One of the reasons is this why the
- 03:45the why that people who are minority
- 03:47scientists enter this field is to
- 03:50help address health challenges
- 03:52of their own communities,
- 03:55and so the topic choice in papers recently
- 03:57published by the NIH about their own grants,
- 04:00shows that awards to African American
- 04:02and black scientists are prohibitively
- 04:04low because of the topic choice of
- 04:06addressing the health disparities
- 04:08that plague their own communities.
- 04:10And this.
- 04:11Makes no sense,
- 04:12right?
- 04:13This makes no sense,
- 04:14but recruiting people into science to
- 04:17address the problems that other people
- 04:19can address and then pushing them out
- 04:21by not allowing them to have funding.
- 04:23So these are both very excellent papers
- 04:25for anyone who is interested in this
- 04:28topic and wants to read more about it.
- 04:30So this lack of representation in
- 04:32science and medicine is a primary
- 04:34driver of health disparities.
- 04:35Just recently,
- 04:36if we highlight the COVID-19
- 04:39pandemic the underrepresentation
- 04:41in science is exactly reflected by the
- 04:43numbers of deaths of COVID-19 with black
- 04:46Americans having the highest rates of
- 04:49death and the lowest representation.
- 04:51This is the same across all chronic diseases,
- 04:54including cardiovascular disease,
- 04:56hypertension, diabetes, and and also cancer.
- 05:01So here in Philadelphia,
- 05:03our demographics are flipped from the
- 05:05predominant demographics in science,
- 05:07where 70% of US faculty research
- 05:11scientists are white. In contrast,
- 05:14only 5% or fewer are African American or
- 05:17black in the school district of Philadelphia.
- 05:20This is opposite, so our predominant
- 05:23populations are black and Hispanic,
- 05:25and these students essentially have no
- 05:27chance of achieving a research career
- 05:30given the predominant prevailing culture.
- 05:33So this is something that we want to change.
- 05:35This first of all,
- 05:36is not fair and second of all,
- 05:38puts people in a situation if they
- 05:40don't even try to pursue science
- 05:42because they know they have no chance.
- 05:44And our goal is to try to help Philadelphia
- 05:46address these health disparities in COVID-19,
- 05:48cancer, diabetes,
- 05:50and Alzheimer's that are are really
- 05:54destroying their communities.
- 05:56So how are we going to do this?
- 05:58We already know that 77% of college students
- 06:02switch out of STEM majors after one semester,
- 06:04we created a program where 72% of
- 06:07our graduates actually continue
- 06:09conducting paid research in college
- 06:11completely flipping these numbers.
- 06:14Fewer than 6% of Philadelphia and other
- 06:17inner city students complete their
- 06:19stem degrees with fewer than 10% of
- 06:21those completing graduate degrees.
- 06:23In contrast, 100% of our students
- 06:26complete their stem degrees on time.
- 06:28So how do we do this?
- 06:29This is a big change, right?
- 06:31A big change.
- 06:32So we created a program
- 06:35built on citizen science.
- 06:37So a staircase of discovery
- 06:39is comprised of four steps.
- 06:41Which level one is crowdsourcing,
- 06:43and many people have heard of apps where
- 06:45people can measure clouds, and you know,
- 06:47say how many animals they saw.
- 06:50In the woods near their house.
- 06:51So it's sort of like like an observation
- 06:54where the data gets transmitted back
- 06:56to scientists who interpret it.
- 06:58The second level is distributed intelligence,
- 07:00so this the citizens can actually
- 07:02collect the data and start to
- 07:04think about what it means.
- 07:05Then participatory science,
- 07:07where the students or participants
- 07:11define the problems that participate
- 07:13in the data collection,
- 07:14and then finally where they're basically
- 07:17independent scientists like like all of us.
- 07:19So we created a program that
- 07:22matches these steps,
- 07:23starting with students as
- 07:24young as fifth grade.
- 07:26So our primary participants
- 07:27are 5th to 12th grade.
- 07:29They start in school,
- 07:31they do their first research
- 07:32experience in school,
- 07:33then they can continue focusing on a
- 07:37junk food diet more in their classroom,
- 07:40summer camps and undergraduate bridge to
- 07:42research that's built on a graduate rotation,
- 07:44and finally independent
- 07:46research and foxchase labs.
- 07:48And by the time they're ready
- 07:49to go to college.
- 07:50Remember,
- 07:50this is just before college.
- 07:52They already have up to two years of
- 07:55research experience under their belt
- 07:57and tend to get paid research positions
- 07:59their first year of college,
- 08:00and then they go up from there.
- 08:04So we started this program in 2013.
- 08:06This is Darius well and she's the science
- 08:09educator, curriculum guru genius,
- 08:11who created basically translates how we
- 08:14do Advanced Research into something that
- 08:16can be done in high school classrooms.
- 08:20And since 2013 we've trained over
- 08:222000 students using this method.
- 08:25This is 570 of them on the steps
- 08:27of the Franklin Institute,
- 08:28where they came to present their
- 08:30Cancer Research data in 2019.
- 08:33As a collective group sharing with each
- 08:36other with scientists with the community
- 08:38that there are 18 new cancer gene
- 08:41hits of nutrients that affect cancer.
- 08:43We're also collecting tons of education,
- 08:45data points, and 60% of these new
- 08:49scientists are underrepresented.
- 08:51Currently in biomedical research.
- 08:54So does it actually work?
- 08:56Do the students want to continue so this
- 08:58is a kind of a complicated diagram,
- 09:00but just focus on the the Blues and the Reds,
- 09:03which are the bad things, right?
- 09:04You don't see much blue and red
- 09:06in any of these pie charts,
- 09:07indicating that the students make
- 09:09tremendous gains in life skills,
- 09:11including peer collaboration,
- 09:12confidence adjusting to projects,
- 09:14and thinking outside the box that
- 09:16they can apply to any career.
- 09:17And keep in mind that these students
- 09:19are unselected.
- 09:20This is a bunch of 9th, 10th,
- 09:2111th and 12th graders who are taking a class.
- 09:24Their teacher decided to participate
- 09:26in the program.
- 09:27They are not pre selected or filled out.
- 09:29An application saying they're
- 09:30interested in science,
- 09:31so this is actually a fairly.
- 09:35A fairly huge gain.
- 09:37He also made gains in research skills,
- 09:40how studying the topic
- 09:41addresses real-world issues,
- 09:42which is something that's
- 09:44incredibly important given the
- 09:45COVID-19 pandemic and other issues.
- 09:48How to formulate a hypothesis,
- 09:49explain projects and and prepare
- 09:51and present their work and then
- 09:54finally the the most important part
- 09:56perhaps is inclusion and interest,
- 09:59whereas students think and feel
- 10:01like a scientist.
- 10:02We have a little work to do on
- 10:04feeling like part of the scientific
- 10:07community to make sure that that
- 10:09that number that red bar goes down
- 10:11and then this was something that we
- 10:13never in a million years expected.
- 10:14We sort of expected.
- 10:16Maybe 20% would be interested
- 10:17in being a scientist.
- 10:18But 56% saying maybe was mind blowing, right?
- 10:22Think about all of the things
- 10:24these kids could be and now just
- 10:25from this one little experience,
- 10:26they're thinking.
- 10:27Maybe I want to be a scientist and even more,
- 10:30the numbers are even higher for
- 10:31students who want to do more research,
- 10:33emphasizing the disconnect between
- 10:35what students think of as science
- 10:38and now what they know as research.
- 10:41So in 2019 we had over 1000
- 10:44students in one run,
- 10:45our biggest auditorium at Fox
- 10:47Chase only holds 320 people.
- 10:49So we created a nonprofit organization
- 10:52called the E close Institute,
- 10:54which is a hub where students,
- 10:57teachers, scientists,
- 10:58community,
- 10:58and hopefully we'll be building
- 11:01accessible databases for everyone,
- 11:03come together to try to solve
- 11:06these community health problems.
- 11:08So we have summer camps where
- 11:11students participate for a
- 11:13week, really delving into
- 11:14high level techniques,
- 11:16including running gels, doing microscopy,
- 11:19lots of pipetting and measuring skills.
- 11:23And in in the summer camps again,
- 11:25more even more students want to be
- 11:28scientists with nobody saying they no.
- 11:30Nobody said no,
- 11:31I don't ever want to be a scientist.
- 11:33And 90% of the students
- 11:35want to do more research.
- 11:36And so one of the things I think we
- 11:38need to think about in general is how to
- 11:41infuse research into more other subjects.
- 11:43Because the students love doing the research,
- 11:45even those who don't necessarily
- 11:47want to be scientists.
- 11:49So this is our undergraduate
- 11:50bridge to research.
- 11:51This is actually where we started
- 11:52in 2013 and we have 230 students
- 11:55who've now completed this program.
- 11:58They have started to grow up
- 12:00now since we started in 2013.
- 12:02We have 16% in medical school
- 12:05and absolutely shocking 17.3%
- 12:08pursuing PHD's in biomedicine.
- 12:11We have a number of them who are doing
- 12:14gap years in research labs 22 percent,
- 12:1718% are engineers and 6%.
- 12:19Are in other stem related careers,
- 12:21especially business entrepreneurship,
- 12:24math type stuff?
- 12:27So yeah,
- 12:27so since this has been working so well,
- 12:29we expanded this to be true
- 12:31community science.
- 12:31Having an out outreach citizen science
- 12:34event in the fall where we had church
- 12:38members and kids and families.
- 12:40Oh that's all blurry,
- 12:42all participating in providing
- 12:44their thoughts,
- 12:45their ideas and their input and how
- 12:48to solve the problem of diabetes.
- 12:51And in the Philadelphia community.
- 12:55So how does this all work? Like?
- 12:56Why is this working better than other
- 12:58things and the the key thing is the Y.
- 13:01So this is a. This is a a video of
- 13:04one of our presenters that emphasizes
- 13:08the importance of the why this
- 13:10project I was most interested in
- 13:12studying squamous cell carcinoma,
- 13:14which is a type of skin cancer that affects
- 13:16over a million people in the US every year.
- 13:18One of those people was my grandmother
- 13:19who I lost to disease in 2015.
- 13:21You might notice a small blue butterfly
- 13:23floating around front presentation,
- 13:24that's why. Joining us today.
- 13:28So one of the most important things
- 13:31for our students is that they are
- 13:33here to cure somebody they love,
- 13:35and so one of the things I think
- 13:37we lose sight of as scientists
- 13:39in our training is is that why?
- 13:41So we come in? Oh yeah,
- 13:43that's great that you came in
- 13:45because your your zeami is sick.
- 13:47But here's how we do things here.
- 13:48Here's the project I'm giving you
- 13:50and so this is something I want
- 13:52everybody here to really start
- 13:54thinking about is do you know what
- 13:56the why is for all of your trainees?
- 13:58Does it matter right?
- 14:00Is that why they're still here?
- 14:01Is that what's driving them to
- 14:03succeed in a very difficult,
- 14:05particularly funding environment?
- 14:06And is that something that that can be
- 14:10leveraged to identify new ways to treat,
- 14:13you know,
- 14:14treat and prevent cancer or other diseases?
- 14:17So diet is a particularly accessible.
- 14:20Topic for children.
- 14:21Everybody knows what's good to eat,
- 14:24what's bad to eat.
- 14:26Children in particular have body image
- 14:28challenges and then many people in
- 14:30their families also have more advanced
- 14:32diseases like diabetes and cancer
- 14:34that they want to understand and help.
- 14:36So we start with the question
- 14:39of what should I eat?
- 14:40Our main goal is to improve research literacy
- 14:42so that students understand what research is,
- 14:45how it's conducted,
- 14:46what the vocabulary is,
- 14:48what's expected of them and including that.
- 14:51The existing hierarchy.
- 14:53So the the program is student centered,
- 14:55it's transdisciplinary.
- 14:56It promotes self efficacy of each
- 14:59and every student and it improves
- 15:01the agency of the instructors and
- 15:04the students to take charge of their
- 15:06own research questions and projects.
- 15:11So why diet? Why does diet matter?
- 15:14You know my my research lab
- 15:16works on how nutrients impact
- 15:18signal transduction pathways,
- 15:19which is the core of how we
- 15:22started and in this area.
- 15:24For this large scale outreach program and
- 15:27diet is unambiguously a key to health,
- 15:30so this is a current sort of
- 15:32diagram of the recommendations for
- 15:33a healthy diet where you have.
- 15:36Lots of fruits and vegetables.
- 15:38Probably too many grains.
- 15:39A small amount of of meat and
- 15:42protein products and some dairy
- 15:43with a very tiny little pie.
- 15:46Slice of junk food here.
- 15:48And I think most people
- 15:50don't really eat this.
- 15:52Most people.
- 15:52It's a little bit expanded down
- 15:54here on this end and reduced
- 15:56a lot here on this end,
- 15:57but this type of healthy diet
- 15:59is known to reduce the symptoms
- 16:01of aging and to promote healthy
- 16:03aging throughout the lifetime.
- 16:05So we all know, right?
- 16:07We all know what we should be eating,
- 16:08but we don't always do that.
- 16:10So what do we do? How do?
- 16:11How do we make this better?
- 16:13There's diets.
- 16:14Dietary cookbooks that are about longevity,
- 16:18reducing calories, eat less,
- 16:20live longer, and this.
- 16:22These diets are actually very,
- 16:24very well supported by basic
- 16:25science data showing that in every
- 16:28Organism caloric restriction extends
- 16:30lifespan and improves health.
- 16:33Most recently, intermittent feeding.
- 16:35Is is another,
- 16:38probably much easier way to reduce
- 16:41the the metabolism challenges that
- 16:43occur during unhealthy aging in a
- 16:46similar way to caloric restriction and so,
- 16:49so how do we leverage these types of diets?
- 16:52Is intermittent feeding a good thing for
- 16:54for a young teenager with a body image issue?
- 16:57Probably not.
- 16:57So how do we start to have the conversations?
- 17:00How do we promote health through
- 17:02diet and how do we leverage chemicals
- 17:04in the diet to try to improve?
- 17:07Existing therapies so another really cool
- 17:09thing about diet is it's very cultural,
- 17:11so every religion has very
- 17:15specific dietary recommendations.
- 17:17There is herbal medicine that is widely
- 17:19used in almost all areas of the world
- 17:22and then just think about where you're from,
- 17:24right?
- 17:25So there's some kind of a cultural
- 17:27cuisine where you're from.
- 17:28That is something that's to
- 17:30be celebrated in holidays.
- 17:31And all of these things,
- 17:32so why not celebrate those
- 17:34same things to promote health?
- 17:38So in the United States,
- 17:39a lot of people do.
- 17:40The herbal medicine type thing
- 17:43using dietary supplements,
- 17:44and just as a as as a thing to note,
- 17:47dietary supplements are
- 17:49not regulated by the FDA.
- 17:51The FDA is not authorized to
- 17:53review dietary supplement
- 17:54products before they are marketed,
- 17:56and so we are relying completely
- 17:58on manufacturers and distributors
- 17:59to make sure the products are
- 18:01safe before they go to market.
- 18:03So no, dietary supplements are
- 18:05regulated by the government.
- 18:0770% of cancer patients are
- 18:08using dietary supplements.
- 18:10Compared to 56.6% of the general population,
- 18:13this is an extraordinarily high number.
- 18:16These studies were done on
- 18:18predominantly white patients with
- 18:20very few I couldn't actually
- 18:22find any studies that were done
- 18:24exclusively on minority patients.
- 18:26The one study I did find said
- 18:29that 76.3% of Hispanic patients
- 18:30do not tell their doctor that
- 18:32they're taking the supplements,
- 18:34which I think is true for most people.
- 18:37So this is something that's
- 18:39also important to.
- 18:40Consider is that people are
- 18:42taking stuff that might be
- 18:44interrupting the the therapy
- 18:46that they're being prescribed.
- 18:48So what's our goal?
- 18:49Our goal is to understand how every
- 18:51chemical that you can consume as part
- 18:53of a diet impacts signal transduction
- 18:55pathways that are involved in disease.
- 18:58So this is a proteome diagram from Joseph LA.
- 19:02So the entire Drosophila genome.
- 19:06Translated into proteins
- 19:07with interaction maps here.
- 19:09So what we would like to do is
- 19:11take each and every compound that's
- 19:13found in the diet and identify those
- 19:15that inhibit or activate individual
- 19:17proteins to create a new diet map
- 19:20on top of the proteome map so that
- 19:23we can create tailored diets for
- 19:25individual diseases based on the genetics,
- 19:28the protein expression,
- 19:30and the the dietary access of the patient.
- 19:34So that's obviously an
- 19:36extremely daunting task,
- 19:37like it's something where our usual
- 19:39one protein one project 1 mechanism,
- 19:42one person is not going to work,
- 19:44and so this is one of the reasons
- 19:47that we think that.
- 19:48Getting high school students involved,
- 19:51which is a population that's
- 19:53eager and in desperate need of
- 19:55having these types of experiences.
- 19:57We have 16 million high school
- 19:58students in the United States
- 20:00with fifty 550 million worldwide.
- 20:02So suddenly a daunting task maybe
- 20:04becomes a little bit more feasible.
- 20:06Each of these students comes from
- 20:08a family that eats right.
- 20:10They have their own particular types
- 20:12of cuisine that are important to them,
- 20:14some of which may have chemical
- 20:17compounds that can inhibit.
- 20:18Cancer signaling pathways to enhance
- 20:21the efficacy of existing therapies.
- 20:25So how do we do this?
- 20:27We have a bunch of dietary supplements or
- 20:29other things that the students bring in.
- 20:32We feed them to fruit flies,
- 20:34either wild type fruit flies or flys
- 20:36bearing mutations in oncogenes,
- 20:38tumor suppressor genes,
- 20:39or more recently in pathways
- 20:41related to diabetes.
- 20:43And then we screen to see what happens to
- 20:45the developmental life cycle of the fly.
- 20:47So do they continue to lay eggs?
- 20:49Do they develop into pupae and
- 20:52then do they close as adults?
- 20:55And So what we found is the most
- 20:57reproducible assay is counting the the
- 20:59number of pupae on the side of the vial.
- 21:02So you can see here.
- 21:03These are like the little larvae,
- 21:04and then they crawl up and become pupa
- 21:07like a chrysalis for a butterfly.
- 21:10And if we have hundreds of people
- 21:13scoring the same exact sample,
- 21:15we actually get pretty tight.
- 21:17Pretty tight statistics for
- 21:19determining the the numbers of pupae,
- 21:22and so you can clearly see that
- 21:24wild type can be compared to loss
- 21:26of function mutants in P-10,
- 21:27which are fairly similar to gain of
- 21:30function mutants in PI3 kinase which
- 21:32are in the same related pathway.
- 21:34Things like the FOXO mutants have
- 21:36much more broad variability,
- 21:38so it's going to be a little
- 21:40bit more difficult to interpret.
- 21:41The results of those experiments,
- 21:43so this type of experiment could
- 21:44be done with any gene that anybody
- 21:46is interested in,
- 21:47for which there is a mutant in the fly model.
- 21:52So we focus with the students initially
- 21:55on basics, so signal transduction.
- 21:56You have a leg and you have a receptor.
- 21:59You have an effect.
- 22:00Are you drive proliferation
- 22:01that causes cancer?
- 22:02Keep it simple and a cancer passed away.
- 22:04You could have too much lag and
- 22:06that drives the whole pathway.
- 22:07You can mutate the receptor or
- 22:08you can have a mutant effector,
- 22:10all of which will give the same outcome
- 22:13of having too much proliferation.
- 22:16So it since 2013 we've had a big
- 22:19project on the EGF receptor pathway and
- 22:21all of the genes that you see here.
- 22:24We have representative viable mutations
- 22:26and flies which are modifiable.
- 22:29Meaning if a compound makes the
- 22:33phenotype worse, that will be detected.
- 22:35If the compound makes the phenotype better,
- 22:37that will be detected because these are
- 22:39mutants that are not complete nulls,
- 22:41so the the great thing about this is
- 22:43that many high schools have eight
- 22:45groups of students who are doing experiments.
- 22:48Together so we give them sequential
- 22:50mutants in the EGF receptor signaling
- 22:52pathway.
- 22:53Have them screen the same drugs
- 22:55and in doing so we can map exactly
- 22:58which of the components of the
- 23:01signaling pathway are affected.
- 23:05So in order to approve the
- 23:07proof of principle for this,
- 23:08we started by treating flies with gefitinib,
- 23:11which is an inhibitor of the EGF receptor,
- 23:14and what happens is the same thing that
- 23:16happens if you have a loss of function,
- 23:18EGF receptor mutant, which is you
- 23:20fuse these respiratory structures
- 23:22called dorsal appendages on the egg,
- 23:25so in a wild type there are two
- 23:26and in a in a gefitinib treated
- 23:28or an EGF receptor mutant.
- 23:30There's only one.
- 23:32So this is a very robust,
- 23:33easy to score phenotype for anybody,
- 23:35just even using a magnifying glass.
- 23:37And then we screened a bunch of
- 23:40different kinase inhibitors and
- 23:41the ones in red are known, e.g.,
- 23:43F receptor inhibitors and you can see
- 23:45that all of them had some effect on
- 23:48induction of dorsal appendage fusion.
- 23:50There were a couple others imatinib
- 23:52which inhibits ABL kinase and miss
- 23:55it nib which inhibits VEGF receptor.
- 23:58Also had had effects which is something
- 24:00will follow up at some time later.
- 24:02Uhm, we also noticed that at a
- 24:06low dose of gefitinib you have
- 24:07the dorsal appendage defects,
- 24:09but normal numbers of eggs.
- 24:10If you increase the dose now,
- 24:12you reduce the numbers of eggs,
- 24:13which turns out to be a much more
- 24:15easy and robust to score phenotype,
- 24:17which is loss of development.
- 24:20And then finally,
- 24:22there's excellent reagents for
- 24:24measuring downstream signaling,
- 24:25including Erk activity,
- 24:26so here is no good fit in.
- 24:28If you see nice Erk activity and
- 24:30as soon as you start adding the
- 24:32gefitinib you you inhibit the Erk
- 24:34downstream of the EGF receptor
- 24:36and you know these are like the
- 24:38students learn how to do this and
- 24:39they do it once and so you get some
- 24:42variability in the loading but.
- 24:44At the end of the day,
- 24:45what we're looking for is something to
- 24:47pursue in a professional lab down the road.
- 24:50So once the students started
- 24:52screening the dietary supplements,
- 24:53the first thing that popped
- 24:55out with Selena methionine,
- 24:56which gives an EGF receptor like
- 24:58phenotype of a single dorsal appendage.
- 25:00You also see dramatically reduced
- 25:03numbers of pupil pupil cases,
- 25:05meaning that the Salina methionine
- 25:07is behaving like a high dose of
- 25:09gefitinib innocence of reducing
- 25:11the numbers of eggs laid.
- 25:15So in order to figure out if this was real,
- 25:17so one student doesn't mean it's right,
- 25:20they could have killed everything, right?
- 25:21Like you, you just don't know.
- 25:23So we put this into a classroom project.
- 25:26For this 570 students I showed
- 25:27you on the steps of the Franklin
- 25:30Institute and they screened.
- 25:32All of the steps in the EGF
- 25:35receptor signaling pathway.
- 25:37Mutants in all of these different
- 25:39steps for effects by selenium and
- 25:41what we see is that the high dose of
- 25:45selenomethionine basically affects everybody,
- 25:47meaning it's probably toxic for any fly,
- 25:50but the low dose was actually quite
- 25:52variable such that only rats and Corkscrew,
- 25:55which is the fly homologue of
- 25:57the tyrosine phosphatase SHP two,
- 25:58were the only two affected and they
- 26:00were affected in opposite ways.
- 26:02Such that the wrasse mutants were
- 26:04less viable and the Corkscrew mutants
- 26:07were more viable upon treatment
- 26:09with Selena methionine.
- 26:11So then we use the Erk activation again.
- 26:14Here's wild type.
- 26:15This is the activated EGF receptor
- 26:17mutant you see a dramatic increase.
- 26:19We can also do this by immunostaining
- 26:22to see specifically which cells
- 26:25are affected by various treatments
- 26:27and what we found here is that
- 26:30the which was a surprise.
- 26:32We expected the Salina methionine
- 26:34to reduce the arc activity instead.
- 26:36If you compare the wild type here
- 26:38in lane one to this lane over here,
- 26:41this Lena methionine.
- 26:43Actually blasted the Erk signaling bypassing
- 26:47any type of inhibition of VEGF receptor so.
- 26:52This turned out to be true in
- 26:54multiple different cancer cells,
- 26:55which the students went on to do
- 26:57in foxchase labs in the summer.
- 26:59So breast cancer,
- 27:00colorectal cancer,
- 27:01and pancreatic cancer with
- 27:02gain of function RASP mutations
- 27:04all showed the similar effect,
- 27:06with SELENOMETHIONINE actually increasing
- 27:08Erk activity up until at least in
- 27:12two cases the dose got too high.
- 27:14On K CO2 which is a non rast dependent
- 27:17colorectal cancer cell line had less
- 27:19of an effect suggesting that like in
- 27:22the fly the gain of function wrasse
- 27:25mutations make the the cells more
- 27:28sensitive to this Selena methionine effect.
- 27:31So we've done this with it.
- 27:32We're still in the process of
- 27:34finishing finishing this project.
- 27:36Over 300 students have worked on it,
- 27:39in addition to the 1001 students who
- 27:41did the screening in the classrooms.
- 27:43So it's going to be a lot of authors
- 27:46on the paper that we're planning
- 27:47to publish this year,
- 27:48but we have a number of other
- 27:50compounds that inhibit specific
- 27:51components of this pathway,
- 27:52so burdock root is a very potent
- 27:55inhibitor in this case of AKT.
- 27:59Butcher's Broom is an activator of Corkscrew,
- 28:02as is Selena methionine and grape seed
- 28:06extract inhibits raft, so so this is
- 28:09something where you can see like.
- 28:10Eventually we will kind of have a a really
- 28:13nice map of this particular pathway and the
- 28:15different compounds that that can affect it.
- 28:18So this was a project that I
- 28:20designed thinking it's accessible.
- 28:22It's easy, it's straightforward.
- 28:23It's part of the curriculum for the students.
- 28:26What they need to learn in high school,
- 28:28and then we started having students
- 28:30come in with their own ideas.
- 28:31So one student brought in apricot seeds,
- 28:33which is mom who was a breast cancer
- 28:36survivor was taking as God's cure for cancer.
- 28:39It turns out as soon as you digest this,
- 28:41it turns into a molecule of cyanide
- 28:43and a molecule of benzaldehyde and
- 28:45women who are taking this are dying
- 28:48of cyanide poisoning.
- 28:49So this is a really serious public
- 28:51health issue that nobody reports to
- 28:52their doctor 'cause as soon as you tell
- 28:55your doctor I'm taking apricot seeds,
- 28:56they say you can die from cyanide poisoning.
- 29:00So, so this is something that's
- 29:02essentially people taking poison
- 29:04that needs to be addressed.
- 29:06Another student came in.
- 29:07Saying that her grandfather had stage
- 29:09four lung cancer and was eating 100
- 29:11live weevils in a glass of Sprite
- 29:14every day and it cured his stage.
- 29:16Four lung cancer and so this is,
- 29:19you know,
- 29:19another curiosity like you.
- 29:20Don't just tell people you shouldn't
- 29:22do that like we need to figure this
- 29:24out and it turns out what she found
- 29:26out was that the defense chemicals
- 29:27secreted by these weevils when
- 29:29they get dropped into a glass of
- 29:30Sprite are actually very potent.
- 29:32Chemotherapeutics against lung cancer.
- 29:34So so this is something where
- 29:36there's truth and there's danger.
- 29:38In in the same thing and these are not
- 29:40things that most scientists would be like.
- 29:42Oh let's go investigate weevils so so
- 29:45these are things that are happening
- 29:47in our communities that we don't know
- 29:49about and are extremely important.
- 29:51And finally,
- 29:51just last summer we had a kid come
- 29:53in who was interested in lean,
- 29:55which is a combination of codeine
- 29:58based cough syrup and Sprite.
- 30:00And kids are using this to get high
- 30:02and he was very concerned that his
- 30:04friends who were all doing this because
- 30:07it's healthier than taking drugs.
- 30:09We're going to get brain cancer and
- 30:11so these are the sorts of things that
- 30:13are going on that the students want
- 30:14to research because it's affecting
- 30:16the people they love and we don't
- 30:18want to bring them in and tell them
- 30:21that's not important because.
- 30:22This is important.
- 30:25So this is a project at all.
- 30:28I'll just highlight a lot,
- 30:29which is a a project designed by 5
- 30:32young ladies starting with Eliana here
- 30:34who was doing a cultural awareness
- 30:36project to find out what cancers
- 30:39particularly affect people from Puerto Rico,
- 30:41and So what she found is that Puerto
- 30:44Ricans have an extremely high rate
- 30:46of HPV based cervical
- 30:47cancer. Even though Hispanic
- 30:49girls were more like likely to
- 30:50get vaccinated than white girls,
- 30:52and so this was something that
- 30:54was really bothering her,
- 30:55so most of the studies have been
- 30:57done on HPV types 16 and 18.
- 30:59So here's 8100 cases of this.
- 31:03But it turns out that in
- 31:04Hispanic and black communities,
- 31:06other strains of HPV are more prevalent,
- 31:08and so these are not small numbers.
- 31:11So 1800 from these types,
- 31:14and then another 1200 from these
- 31:16types is is not a small number,
- 31:18and it turns out that many of these
- 31:20strains of the virus are not actually
- 31:22protected by available vaccines,
- 31:24so so this started a conversation
- 31:27among these predominantly minority
- 31:29women of what's going on with this.
- 31:31So there's a lot of.
- 31:34You know,
- 31:35sort of social reasons for for pointing
- 31:37fingers at why health disparities exist.
- 31:40So a lot of it has to do with poverty,
- 31:44access to health care and various
- 31:46life choices that are generally
- 31:49considered explanations for why
- 31:50these health disparities exist.
- 31:52But Eliana's discovery,
- 31:53sort of made it seem like maybe
- 31:56there's some genetic basis
- 31:57to some of these differences.
- 31:59So Nicole Harrington came in
- 32:01with this concept that black
- 32:03mothers don't trust the medical
- 32:05community enough to get vaccinated,
- 32:07and so this is an example for the
- 32:09COVID-19 vaccine where you can
- 32:11see that black Americans had a
- 32:13very very low vaccination rate
- 32:15compared to white Americans.
- 32:17And similarly for the HPV vaccine,
- 32:20the same thing is true where?
- 32:23Hispanic and and black Americans are
- 32:26less likely to get vaccinated and
- 32:28then what we also need to really
- 32:32realize is that they they think the
- 32:35vaccine is harmful and even more that.
- 32:39You know?
- 32:39They think people are being treated
- 32:41like Guinea pigs by scientists like us,
- 32:44so so this is a really big issue
- 32:46in terms of how to get information
- 32:48out how to reduce this mistrust
- 32:50and our take on this is that we
- 32:52need to increase representation and
- 32:55understanding of the fears that the
- 32:58public has about these vaccines.
- 33:02So then we went down to the
- 33:04cellular molecular level,
- 33:05so HPV happens with a.
- 33:08Initial infection,
- 33:09but the virus can move into sort
- 33:13of the the basic sort of stem
- 33:17cell areas of the of the cervix,
- 33:19and then it can just hang out for
- 33:22awhile and then eventually it
- 33:24can come out and create invasive
- 33:27neoplasia and so this is a pathway
- 33:29that's that's basically mediated
- 33:31by inhibition of P53 and RB,
- 33:33which are two proteins that
- 33:35control the cell cycle,
- 33:37and so two students neelys and Allison.
- 33:40Decided to screen dietary supplements
- 33:42to find something that would kill
- 33:44flies bearing mutations in P53 or
- 33:46RB to sort of mimic virus infection
- 33:48and what they found was multiple
- 33:51components that drive a process
- 33:53called ferroptosis which is a
- 33:55type of iron dependent cell death
- 33:57and you can see here that.
- 33:59The P53 null flies are highly
- 34:02susceptible to acetaminophen,
- 34:04which is Tylenol or iron in
- 34:06terms of being killed.
- 34:08And then they went on and did a dose curve
- 34:10to find doses that really had little or
- 34:13no effect on wild type but still were
- 34:15were potent for RB and P53 mutants.
- 34:18And so we're very interested in this kind of
- 34:21idea that they came up with from their own.
- 34:24Experiences, and it turns out that
- 34:27HPV inhibits a receptor that is a
- 34:30major controller of of ferroptosis
- 34:33through a protein called G.
- 34:36PX4P53 is also a regulator of this process.
- 34:38Acetaminophen, which is one of the
- 34:41things that scored in the screen
- 34:43actually affects this whole process,
- 34:45and so a colleague of mine,
- 34:47Jeff Peterson, who's also at Fox Chase,
- 34:49is a lab that studies ferroptosis,
- 34:51and so they had two compounds, ESA.
- 34:54And harassed in that act in different
- 34:56ways to induce ferroptosis.
- 34:59And so we wanted to see.
- 35:01Whether the observations that the
- 35:03students made in the fly would be true
- 35:06also in HPV depending cancer cells,
- 35:08so this was done by Jesse Rynok with
- 35:11the help of postdoc and Jeff Slabtown
- 35:13who sing and what we see is differential
- 35:17sensitivity to the ESA compound,
- 35:20such that in cervical cancer cells,
- 35:23HPV positive cells are resistant to
- 35:25induction of ferroptosis and in the
- 35:27head and neck cancer cells there
- 35:29are actually more sensitive.
- 35:31And so this is something that we're
- 35:33trying to figure out now, like,
- 35:35what is the difference between these?
- 35:36And obviously the cells have more
- 35:38things going on in them other than
- 35:41just HPV infection.
- 35:42But we know that this was actually
- 35:45ferroptosis process because if you
- 35:47add an inhibitor of ferroptosis
- 35:49then you abrogated the the response.
- 35:53So using a different inducer of Ferroptosis,
- 35:57Calder,
- 35:57Aston there didn't seem to be any
- 36:00effect at all on HPV minus head
- 36:02and neck cancer cells,
- 36:04but there really was a dose dependent
- 36:08reduction increase in killing basically
- 36:10of the HPV positive cells that Jesse is
- 36:13going to be further exploring this summer.
- 36:16So the two projects together maybe actually
- 36:20centered on on one particular thing,
- 36:22which is selenium.
- 36:23Uh, which is an activator of GPX 4G.
- 36:27P X4 is a selenium dependent protein that
- 36:29prevents the production of lipid radicals,
- 36:32which are what causes this ferroptosis
- 36:35and at the same time we found
- 36:37that if we reduced Selena,
- 36:40if we increase selenomethionine
- 36:41in the EGF receptor pathway,
- 36:43we drive activity of ERC which we know I did.
- 36:46I didn't show,
- 36:47but it's through Corkscrew S HP2,
- 36:49which happens to also be a a tyrosine
- 36:51phosphatase that's regulated
- 36:52by these lipid radicals.
- 36:54And so one of the things that's kind
- 36:56of coming out just from this initial
- 36:59one single compound that we focused on
- 37:01is maybe there's a vulnerability in in.
- 37:04In these the head and neck cancer cells
- 37:06for for a dependence on selenium,
- 37:08such that if a restriction diet that
- 37:11reduces the levels of selenium is used
- 37:13in conjunction with existing therapies,
- 37:16maybe they'll work better.
- 37:19So all of this is to say that the
- 37:21Y really matters for the students,
- 37:23and the way our scientific culture
- 37:25is set up right now we have a very
- 37:28high level principle investigator.
- 37:29It goes down, down,
- 37:30down depending on the level of training
- 37:32such that high school students are
- 37:34gifted with science and what we would
- 37:36like to do is change that so that the
- 37:38high school students come in with
- 37:40the science they already have that
- 37:41we figure out what those projects,
- 37:43those questions those hypotheses are,
- 37:46and matched them to a scientist who is also.
- 37:48Interested in the same thing and
- 37:50so so that it comes in more as a,
- 37:53you know, appear kind of attack on
- 37:56the same problem and so one of the
- 37:59things I really want to say is that
- 38:00the culture matters and so this is
- 38:02a an image of a boardroom from Time
- 38:04magazine from a little while ago
- 38:06where you can see the top guys are are
- 38:09all up here talking down here to the
- 38:12diversity equity inclusion officers
- 38:13who are supposed to be the ones who
- 38:15are focused on changing the culture,
- 38:18but instead they're being lectured on.
- 38:19This is our culture.
- 38:21And so one of the things that's really
- 38:23important is to consider whether
- 38:25this is your lab meeting, right?
- 38:26If this is your lab meeting and you're
- 38:28not considering the ideas of the people
- 38:30down here at this end of the table,
- 38:32then that's something that's
- 38:34really time to change.
- 38:36Finally,
- 38:36one of the things that's really our job
- 38:39if we take underrepresented students
- 38:40into our lab is to ensure their safety.
- 38:43You need to be the shield against
- 38:46the systemic racism that's coming
- 38:48at them from every direction,
- 38:50every minute of every day so that
- 38:52they can run behind you in a way
- 38:54that they can thrive and bring
- 38:56these new ideas into biomedicine.
- 38:58And finally,
- 38:58like I just want to share my own
- 39:00experience that the way these
- 39:02students think has completely
- 39:04changed the way I think about an
- 39:06important scientific question.
- 39:07Such that the biology,
- 39:09the environment,
- 39:10and the lifestyle all have to be
- 39:12considered so that we can really
- 39:13address particularly health disparities
- 39:15in cancer and other diseases.
- 39:18So I just want to leave you with
- 39:21with our group our crew from
- 39:232019 remember their faces.
- 39:25This is the future of Cancer Research.
- 39:28Isabella,
- 39:29here on the right side is just
- 39:31got accepted to a Yale summer
- 39:34program and she's considering that,
- 39:36and I think 14 other other programs so,
- 39:39so we'll see whether she comes.
- 39:41So we've had a bunch of funding,
- 39:43a lots,
- 39:44lots of support that we're
- 39:45particularly excited about.
- 39:46A recent partnership with
- 39:48the American Cancer Society.
- 39:49For the E close programs to
- 39:51support 300 young ladies doing
- 39:53Cancer Research this summer,
- 39:55and the team is amazing,
- 39:57I already mentioned Dara.
- 39:58I have my lab who's who supports all
- 40:01the students summer learning and a
- 40:04whole bunch of foxchase mentors.
- 40:07Yeah, so that's it. Thank you.
- 40:14Thank you so much, Alana.
- 40:16I'd like to ask folks to put
- 40:18questions into the chat,
- 40:20and if you don't I can start off with one.
- 40:24If that's OK with you, then maybe Barbara,
- 40:25I'm sure has questions.
- 40:27So First off that was.
- 40:28That was a fascinating presentation in a
- 40:30real Tour de force that congratulations,
- 40:33a lot of questions about the nuts and bolts.
- 40:35So how do you fund this?
- 40:38How do you channel hundreds of
- 40:40high school students in 220
- 40:43labs at best at Fox Chase?
- 40:46Right,
- 40:47we don't. We can't write.
- 40:49You can't do that. You can't have 2000.
- 40:52I mean, we're we're actually hoping to
- 40:54reach 10,000 students a year by next year,
- 40:56and there's no way that we can put each
- 40:58and every one of those students into a lab.
- 40:59It's just not possible,
- 41:00and so that's what we're trying to flip.
- 41:02So when COVID-19 happened,
- 41:04it became unambiguous that
- 41:06students couldn't come to the lab.
- 41:07And So what we did was we created a hybrid
- 41:10program where we create labs in a box,
- 41:13and we mail them to the students
- 41:15who create the lab in their house.
- 41:17And so, because fruit flies are safe,
- 41:19the dietary supplements are over the counter.
- 41:22Everything that they research
- 41:23is over the counter.
- 41:25That doesn't mean it's safe,
- 41:26but that just means it's legal
- 41:28for them to investigate,
- 41:30and so they they do all of
- 41:32the research in their homes.
- 41:33And so all of the initial.
- 41:36Initial data collection and
- 41:38analysis is is done in a way where
- 41:40we don't actually need any space,
- 41:42so we also train teachers.
- 41:44We have, I think 32 now teacher partners,
- 41:48each training about 100 students a year,
- 41:50and so the teachers now we just we
- 41:54got an award that I don't think
- 41:56I'm allowed to say what it is.
- 41:57But it's really big and exciting.
- 41:59That's gonna pay for building of Eclose
- 42:02Labs in 10 Philadelphia schools this year.
- 42:06And so now the schools will.
- 42:07We each have a fully equipped lab,
- 42:09just like the clothes lab for the
- 42:11students to do the work there.
- 42:13Yeah, so.
- 42:14So yeah.
- 42:14So and then the other thing we did was
- 42:17make it very inexpensive so dietary
- 42:19supplements don't cost very much and
- 42:21flies cost almost nothing and so the
- 42:23cost for for each participant once
- 42:26they have the lab setup is only $15 a kid.
- 42:29So so far we've been able to to do that.
- 42:33The primary driver of the revenue
- 42:34right now and the fund raising is that
- 42:37universities are sponsoring these programs.
- 42:39Everybody sort of wants well trained,
- 42:43underrepresented students to come to
- 42:44their school and so they are paying
- 42:47for us to run the programs for them.
- 42:49Which is,
- 42:49I mean,
- 42:50how could it get better right as
- 42:52a partnership like like we help
- 42:53you get your students ready and
- 42:55and you can get the funding.
- 42:56So so that's how it's been so far.
- 42:59But yeah, funding is always, you know.
- 43:02And then the so most of those
- 43:04Western blots being done in the
- 43:06echoes lab, and I presume that's
- 43:07a physical lab inside Fox Chase.
- 43:09No. So the western blots are done
- 43:11by the students who stay in the
- 43:13summer for the independent research.
- 43:14They get matched into the labs.
- 43:16We we have too many Westerns to
- 43:18do for that to remain feasible,
- 43:20and so last summer we developed a dot
- 43:22blot protocol which I should have put in.
- 43:25They were a little ugly and they
- 43:26weren't related to the projects I was
- 43:28talking about like, but but it works.
- 43:30So so you can do Erk,
- 43:32Erk dot blots that give you the same
- 43:34answer that you get on a Western and
- 43:36you can do them just by pipetting onto
- 43:38a membrane in a high school classroom.
- 43:41And so, so that's what we're sort of doing,
- 43:43is trying to figure out how to kind of.
- 43:45Actually, we could call it kicking
- 43:47at old school, like how?
- 43:48How do we do things before we
- 43:50could do all these fancy things?
- 43:51And then we're bringing those back with
- 43:53the idea that the professional labs
- 43:55will then confirm confirm the results.
- 44:00Barb, Yep.
- 44:02So a lot of amazing work and
- 44:06to touch so many lives it's
- 44:09it's just very inspirational.
- 44:12It's sort of like the the
- 44:13why question, but if you could take
- 44:15us back to when you started this.
- 44:19How did you get the Philadelphia Public
- 44:21Schools to let you in?
- 44:23And were there particular
- 44:25challenges in the beginning that?
- 44:27That if you knew now what you if you knew,
- 44:31then what you knew now,
- 44:32you would have structured a little
- 44:35differently in the beginning.
- 44:35Or how did it? How did it get
- 44:37off the ground to the scale?
- 44:39Yeah, so it it did end, right?
- 44:41We we started with 15 students.
- 44:43Our initial intention was eight because
- 44:45one of the reasons I went to Fox Chase was
- 44:47because they had a high school program.
- 44:49I participated in a program called
- 44:51Project Success when I was a grad student
- 44:53at Harvard and and Ben Neal's lab.
- 44:55And my student was.
- 44:58So extraordinarily smart and
- 45:00so extraordinarily unprepared.
- 45:02And so we spent the whole summer
- 45:04doing a lot of stuff.
- 45:05It it just became very clear that if
- 45:07a student like her instead of getting
- 45:09dropped into a lab like Ben's lab had
- 45:11had a training experience ahead of time,
- 45:14so that she would know how to measure,
- 45:16like know what a gram was,
- 45:18that it would be much different.
- 45:19So I knew that that she's now a chief
- 45:22attending at CHOP in Philadelphia.
- 45:25So extraordinary success.
- 45:26And and I know her and she has
- 45:29two little kids and it's amazing,
- 45:31but but it transformed me a lot more
- 45:33than it did hurt like like this is
- 45:35something where I can put this tiny
- 45:37little bit of effort into this and it
- 45:39can change somebody's whole family's life.
- 45:41So I knew that if I ever got a faculty job,
- 45:43I would want to create a
- 45:45training program ahead of time.
- 45:46So our first year we we trained 15 students.
- 45:49Most of them were not actually
- 45:52underrepresented from Philadelphia.
- 45:53It took us a couple years to figure out
- 45:55that Philly students weren't applying
- 45:56because they didn't think they could compete.
- 45:58With suburban kids,
- 45:59so we created a Philadelphia only section,
- 46:02and since then it's just been exploding.
- 46:04And then it's actually Dara who
- 46:06got into the Philly school system
- 46:08by her connections with teachers.
- 46:09So she was a teacher in the
- 46:12Philadelphia school system before she
- 46:13was a Community College professor.
- 46:15And so she just used those connections
- 46:17and we started getting in.
- 46:18We're not actually throughout
- 46:20the Philadelphia school system,
- 46:21yet we still partner with individual
- 46:24teachers,
- 46:24the inner City Schools are so
- 46:26oppressive to try to get into,
- 46:29and they don't have any money.
- 46:30To pay for STEM so.
- 46:32So we've just accepted that that's
- 46:34our responsibility,
- 46:35and yeah,
- 46:35so now people at you close are
- 46:38writing these grants to to to make
- 46:41sure that our Philly students
- 46:42are our highest priority.
- 46:45Atlanta can tell us a little more
- 46:46about E close. How big is it?
- 46:49How many people work there?
- 46:50How do they relate to Fox Chase?
- 46:53So you close is separate from Fox Chase.
- 46:56It's a separate nonprofit foxchase.
- 46:59Like I said is pretty small and so to run
- 47:01a nationwide program with 10s of thousands
- 47:04of students a year is not something
- 47:07that's that's within that capacity.
- 47:09So so we created it as a separate
- 47:12nonprofit almost our third
- 47:13year anniversary is coming up.
- 47:15We have 21 employees,
- 47:18all of them are part time.
- 47:21Third of them are instructors.
- 47:23A third of them are scientific
- 47:24technicians who build the kits and and
- 47:26and set up some of the experiments
- 47:29depending on what the program is,
- 47:31and then the the rest are.
- 47:34You know, I'm a volunteer,
- 47:35so I just said total volunteer.
- 47:39Yeah, so it's, uh, we're in 14 U.S.
- 47:42states now we have 11 university sponsors,
- 47:46including seven comprehensive cancer centers,
- 47:49the American Cancer Society
- 47:51sponsoring that huge program,
- 47:52and we have programs ranging all
- 47:54the way from 5th grade through
- 47:56through adults interested in
- 47:58transitioning into biomedical careers.
- 48:00So it's a it's a very rapidly,
- 48:03rapidly growing thing,
- 48:05and I think the COVID pandemic when
- 48:08nobody could actually do any science.
- 48:11With you know all of a sudden they're like,
- 48:13wait.
- 48:13I heard about these people
- 48:15who started this thing,
- 48:16so I'm in the equals lab now.
- 48:18It's 500 square feet and it's you know,
- 48:21we'll we'll grow as we grow.
- 48:25There's a question from the
- 48:26audience from Doctor Rose,
- 48:28so are these other resources to help
- 48:30these young people get into college,
- 48:32pay for college, and do you
- 48:34find these issues are barriers?
- 48:37So we don't have those resources.
- 48:39Uhm, like I said, we don't actually
- 48:41even have full time employees yet
- 48:44that that's that's something that.
- 48:48Yeah, I'm not.
- 48:49I'm not sure that we will get there
- 48:51because most of our students end
- 48:52up getting full ride scholarships,
- 48:54so our biggest sending schools at this
- 48:56point are University of Pennsylvania,
- 48:58which has hosted 32 of our senior
- 49:01level students and I don't think
- 49:04any of them has paid and our second
- 49:06biggest sendings will now is MIT.
- 49:09We also have a lot of students at
- 49:12Pitt and Drexel and Temple and I
- 49:14don't think any single one of our
- 49:16students who've gone to Temple has
- 49:18not been assigned scholar, which is.
- 49:20For four year scholarship with
- 49:22room and board,
- 49:23the whole the whole 9 yards.
- 49:25And so I think the unusual nature
- 49:29of having this kind of research
- 49:31experience a personal statement
- 49:34that's talking about how discussing
- 49:36your personal why the person that
- 49:38you did this for and how you are
- 49:41going to bring together all of the
- 49:43interest that you gained from this
- 49:45program into creating a project is
- 49:47going to be transformative is pretty.
- 49:49It's pretty well received by.
- 49:51By colleges and universities.
- 49:53So far so so that may be something where
- 49:56there's another nonprofit that's doing that,
- 49:58like providing scholarships and
- 49:59things we would love to partner.
- 50:01Like I said, it closes a hub.
- 50:03We want to kind of drop down the barriers
- 50:05of competition so we don't really.
- 50:08You know,
- 50:08I've had a lot of people in fly land say,
- 50:11oh,
- 50:11we'll just replicate your program
- 50:12like that's great,
- 50:13but now we're your date is
- 50:14gonna be over there.
- 50:15Our date is what's the point like
- 50:17why don't we do this together so so
- 50:19that's one of the main things we're
- 50:21working on this year is how to.
- 50:23Collect the data so that if somebody does
- 50:25replicate the program just on their own,
- 50:28how is it that they can contribute to
- 50:30the database so that all of us can,
- 50:32you know,
- 50:32use this kind of screening data
- 50:34for for advancement of science.
- 50:37And one of the
- 50:37things that struck me in your talk
- 50:39was that you said multiple times
- 50:41the students decided to do this,
- 50:43that or the other the student
- 50:45was interested in this question.
- 50:47So essentially none of us gets
- 50:49to really choose what we decide
- 50:51to do in science all the time.
- 50:54You have to have funding.
- 50:55It has to be practical and feasible
- 50:57and so on. So when a student.
- 51:02Their shows interest in something.
- 51:03How do you channel them to a lab that
- 51:06might actually have the expertise?
- 51:08See that you don't have endless
- 51:10labs approx chase
- 51:11right? So this this is our that that's
- 51:13like our newest newest thing. So the 1st.
- 51:17Four years, maybe five years of the
- 51:20program was really just my thing.
- 51:22Like let's do EGM perceptor because you know,
- 51:24we had to figure out how to do it all.
- 51:27Does the data even mean
- 51:28anything like thank heavens,
- 51:29the people counting is really,
- 51:30really really significant and important.
- 51:33So, so we spent those five
- 51:34years just doing my thing.
- 51:36So in 2017 we started getting
- 51:37kids bringing in bags of like my
- 51:40mom's eating this and then that's
- 51:42when that started to change.
- 51:43And so it's really only in the past
- 51:46two years where we're trying to.
- 51:48Bring together Foxchase faculty who
- 51:50do specific things so we have behaved
- 51:54social behavioral researcher Carolyn Fang,
- 51:56who's extremely interested
- 51:58in medical mistrust.
- 51:59Who was more than happy to
- 52:01host Nicole in doing this?
- 52:02This project that she's doing and
- 52:04then together we got this small
- 52:06foundation grant for five more
- 52:07students to continue that work.
- 52:09So Caroline, will,
- 52:11you know,
- 52:12support them and developing
- 52:14educational interventions specifically
- 52:15designed for the communities of
- 52:18the participating five members?
- 52:19Of that of that research group,
- 52:21and then Jeff just happened to
- 52:23work on Ferroptosis and we landed
- 52:25on iron and acetaminophen, right?
- 52:27So so so far, it's like coming together.
- 52:29Last summer we had seven students.
- 52:31Everyone from a different cultural
- 52:33background who all were interested
- 52:35in BRCA driven breast cancer.
- 52:37All of them had a family member.
- 52:39We have another group that's
- 52:41interested in beta thalassemia,
- 52:43so a number of different again cultural
- 52:46groups that were interested in that.
- 52:48And so right.
- 52:49This is why.
- 52:50By the concept of eclose is going to
- 52:52become more and more and more important,
- 52:54especially with university sponsors,
- 52:55because where am I gonna send the
- 52:58kids I I'm already way overwhelmed.
- 53:00Like Oh my gosh,
- 53:01I can't think about all of these
- 53:03projects all at the same time,
- 53:05and so that's what we sort of need.
- 53:07And so we're kind of thinking about
- 53:10creating like a fast pitch competition.
- 53:13That's a video based thing
- 53:14where every student would like
- 53:16hold up their phone and go.
- 53:17Oh,
- 53:17and this is the project
- 53:19I'm really excited about.
- 53:19And then the scientists
- 53:21would just go through.
- 53:22You know no more than 30 seconds to a
- 53:24minute pitch and say that student is
- 53:26interested in what I'm interested in.
- 53:28So do you see what I mean?
- 53:29Like we're hoping to kind of like
- 53:31change it so that the students
- 53:33actually can go into a lab.
- 53:35That celebrates their interests.
- 53:36We also I forgot to say we have a
- 53:39partnership with Penn Medicine that
- 53:40takes a number of our students each
- 53:42year and they have they're much bigger,
- 53:44so they they have more capacity.
- 53:49Wow, that's an amazing undertaking.
- 53:51The whole thing. But what percent
- 53:52of your time do you spend on this?
- 53:54Just one last question. Unless Barbara
- 53:56I'm officially allowed to spend one
- 53:57day a week, that's what I spent.
- 54:00OK, we won porcian that yeah.
- 54:04Burp. Any closing coming up?
- 54:07You know I, I just want to say
- 54:11again that the the creativity and
- 54:13the the way you've leveraged what
- 54:16started out as small experiences to.
- 54:18To extend to so many people
- 54:20and and also you know.
- 54:22So I know that at Yale,
- 54:24over 50% of our first generation
- 54:28and underrepresented undergraduates
- 54:30when they show up as first years.
- 54:33Say that they want a major in
- 54:35STEM and the attrition is,
- 54:37as you said,
- 54:38over 70% of of them don't end
- 54:40up graduating in a stem.
- 54:44Programs or major.
- 54:45So the you know the fact that
- 54:47you are seeing 100% retention in
- 54:49STEM and that your medical school
- 54:52PhD balance because you know,
- 54:54we're also aware that minority communities
- 54:57are more familiar with the physician
- 55:00as a role model than the scientist.
- 55:02I think those just they they said
- 55:04a very high bar for everybody
- 55:06else who works in this space.
- 55:07It's amazing.
- 55:08Well yeah, I mean we,
- 55:09you know we could just help you like that.
- 55:11That's one of the things
- 55:12that we I actually met.
- 55:14Tony Koloski at this huge professors
- 55:17competition that we were both finalists
- 55:19there and the goal behind that was
- 55:22to create undergraduate a first year
- 55:26undergraduate semester of doing this.
- 55:28Like doing the program that we
- 55:30designed and so that students
- 55:31wouldn't go into that weed out class.
- 55:33Because every school has a weed out
- 55:36class which I cannot comprehend
- 55:38right at Temple at Temple,
- 55:40which was the partner they
- 55:41say we give them chemistry.
- 55:43We failed.
- 55:4470% of the students and this is
- 55:46like a we did a good job.
- 55:47We failed 70% out and so why would
- 55:49you recruit students who are already
- 55:51vulnerable not based on their own fault,
- 55:54but because of the challenges of an
- 55:56inner city public education and then
- 55:58fail them out like that's basically.
- 56:00You know it's it's so unfair
- 56:02it's basically taking any little
- 56:04tiny step on the rug that you
- 56:05had and yanking it right out.
- 56:07So,
- 56:07so that's what we would be dreaming
- 56:10of having in the future is to be
- 56:12able to work with each and every
- 56:14school to say what's the most
- 56:16important research that you're doing?
- 56:18How do we create interdisciplinary groups to,
- 56:21you know,
- 56:22have a student who's interested in
- 56:23public health together with a student
- 56:25who's interested in chemistry biology.
- 56:27Do you see what I mean to to basically
- 56:29create those kind of program project
- 56:32groups from students as their
- 56:34very first research experience?
- 56:36That's what we really want to do.
- 56:39It's amazing,
- 56:40thank you so much. That was amazing.
- 56:43Incredibly inspiring. Thanks for
- 56:44taking the time to talk to us today.
- 56:47Thanks, thanks everybody.
- 56:49If you have questions,
- 56:51you can find me. Alana Fox Chase.
- 56:54OK.