Myeloid Cells & Mechanistic Insights Into Disease - The Sefik Lab

Transcript

• 00:05Myeloid cells are part of the innate immune system.
• 00:09These are the most abundant cells we find in circulation,
• 00:12in blood as well as in tissues.
• 00:14So we study them because they're involved in all processes.
• 00:17They're the first responders,
• 00:19but they don't leave when things go out of control, they stay,
• 00:24and we think they're primary drivers of the disease
• 00:27and instruct other cells as well to drive disease.
• 00:34We study infectious, inflammatory and autoimmune disease in the lab,
• 00:38and we're trying to understand how immune cells drive pathologies and disease.
• 00:43And the focus primarily is myeloid cells.
• 00:46So we study monocytes, macrophages and neutrophils,
• 00:48and we study how these cells drive disease.
• 00:51We follow them to the course of a disease.
• 00:54Trying to find more human relevant models where we watch a disease progress,
• 01:00learn from it, then go back and perturb it
• 01:03and learn from that perturbation and try to gain a better understanding
• 01:06so that we can make better drugs treating disease.
• 01:13So conceptually we start with human data.
• 01:15So we pick a disease.
• 01:17It could be fibrosis.
• 01:18It could be cancer.
• 01:19It could be infectious disease.
• 01:21We did a lot of work with SARS-CoV-2 infection in COVID-19.
• 01:25We start with the human data
• 01:26and based on this observational data,
• 01:29we make a hypothesis that we are going to test in a mouse model.
• 01:34We have something called humanized mice.
• 01:36This work was pioneered by my mentor Richard Flavell two decades ago,
• 01:41and I have been building on it to improve the types of cells we have.
• 01:45The unique aspect of this mouse is it has genes,
• 01:48human genes that are necessary for human immune system to develop.
• 01:52On top of a human immune system,
• 01:54we have also provided tissue cells to these.
• 01:56So they have a liver that is humanized.
• 01:59We have humanized the lung.
• 02:01We have humanized the intestine, and we have humanized the skin.
• 02:06So now we have a system where we can study human cells
• 02:10in the context of any type of disease.
• 02:13We study them, we start perturbing or identifying networks that are driving
• 02:18and we block those networks.
• 02:19We take them out of the equation and see if they matter.
• 02:21If they don't matter,
• 02:22then we go back to the human data and try to come up with better hypotheses.
• 02:27If they matter, we still go back to the human data
• 02:29and see if there is any sign there that you know, encourages us to keep working.
• 02:38So, I do basic science,
• 02:40but I hope that one day
• 02:42findings that we found in the lab are gonna help someone.
• 02:48So before something is a candidate for drug development,
• 02:52we need to study it in a human relevant system, hence our mice,
• 02:56and do this iterative work where we go back and forth with human data,
• 03:01mouse model, human data, mouse model and gain a true mechanistic understanding.
• 03:06And once we have a strong candidate
• 03:09after really hard work, then we try to take it to clinic,
• 03:13and I think the way we're doing our research
• 03:16will allow us to go to clinic with better candidates
• 03:20and also maybe make it faster
• 03:23so that what we find on the bench doesn't take 20 years for it to go to clinic.