Rimm Lab Marks 30 Years of Research, Innovation, Training at Yale Pathology

As principal investigator of the Rimm Lab at Yale School of Medicine, David Rimm, MD, PhD, Anthony N. Brady Professor of Pathology and professor of medicine (medical oncology) doesn’t dwell much on the past. His lab is always looking forward, working on the next diagnostic test to find the best way to bring the right drug to the right patient.

But Rimm did look back recently as the Rimm Lab marked 30 years of research and innovation at Yale. Over the past three decades, Rimm and lab members have published hundreds of scientific papers, obtained several patents, and focused on quantitative pathology using technologies invented in the lab. In fact, last year, Yale Pathology Labs introduced the new Troplex™ assay, developed in the Rimm Lab, to quantitatively measure the levels of two breast cancer biomarkers, HER2 and TROP2, which are targets for antibody-drug conjugate therapies.

Despite those successes, Rimm says what matters most are the people who have passed through his lab over the years. They number more than 140, including technicians, undergraduates, and medical students. His twentieth graduate student mentee is on track to graduate next year.

“So, over the years, I have trained 20 graduate students and 53 postdocs – 73 scientists who are out there who think like I do,” Rimm says. “This is my proudest accomplishment. It’s one thing to do rigorous science, but to me, it’s more important to replicate rigorous science to the people you’ve trained.”

Among his trainees are Kurt Schalper, MD, PhD, associate professor of pathology at Yale, and Elsa Anagnostou, MD, PhD, the Alex Grass Professor of Oncology at Johns Hopkins School of Medicine, not to mention other trainees in Ireland, Spain, Sweden, Greece and China. One of his trainees, Mark Gustavson, leads a pathology analysis group at AstraZeneca, while another, Jena Giltnane, worked in pathology at Genentech for several years.

“I’m trying to stress the philosophy that pathology needs to be quantitative, not entirely subjective. There are subjective parts that will never go away. But the parts that we can make quantitative, we should make quantitative, and that’s been my underlying vision,” he says.

Rimm’s philosophy can be summarized in three words: Measure, don’t read.

“The people who I have trained over the years all know that, and they’re moving that vision forward,” Rimm says. “Your trainees really represent your contributions as much as anything. You can write a bunch of papers – I have close to 600 – but they probably don’t make as much difference as the fact that there are 73 or more scientists out there who share my vision and philosophy.”

Marisa Dolled-Filhart, PhD ‘05, who was Rimm’s second graduate student from 2000-2005, describes her five years in the lab as “wonderful and intellectually special” because of the effort Rimm put into her development as a scientist.

“The research areas I focused on inspired my career in precision medicine and oncology, where I’ve had the ability to impact cancer patients by contributing to developing drugs and diagnostic tests currently used in oncology clinical practice,” says Dolled-Filhart, who now leads oncology drug development teams at Daiichi Sankyo and held prior precision medicine and translational biomarker roles in biotech at CRO, Merck, and BMS.

“Dave has always been at the leading edge of quantitative pathology and precision medicine, with a focus on impact for cancer patients. I have been amazed to see how many of the students, postdocs, and fellows have remained passionate about, and have dedicated their careers to, these areas.”

In fact, she says Rimm’s unwavering dedication to his students inspired her to mentor others at work, as a board member of the Yale Graduate School of Arts and Sciences Alumni Association Board, and through Yale Cross Campus, an online Yale networking and mentoring program for students and alumni.

“I continue to be passionate about paying it forward by mentoring students and earlier career scientists. I do this because I truly understand the importance and impact of a mentor from Dave – as an example and a role model.”

Some 40 years ago when Rimm was applying for Johns Hopkins University School of Medicine, he recalls telling interviewers that he one day hoped to have a career doing work that affected patient care but also had a scientific content. When he first started at Yale, Rimm was signing out in cytology 50% of his time. But he was advised that if he could get grants, he could reduce his clinical sign-out. Around 2002-2003, Rimm did the pivotal work in determining how to quantitatively analyze tissue. He and then-lab member Robert Camp, MD, PhD, associate research scientist in pathology, wrote a paper that introduced a new approach to tissue analysis. That resulted in funding, allowing Rimm to train all those scientists, and no longer do clinical sign-outs. “That’s what propelled the lab,” he says.

The lab has been fortunate to receive consistent funding from the Breast Cancer Research Foundation, which, Rimm says, has enabled him to train students. Biotech and pharma also provide funding for the lab, which seeks to find the right drug for patients.

“Patients are so different, so you have to assay the patient, either the whole patient, or what we specialize in, the tumor tissue, and figure out what the biology is, and how that biology can match up with the drugs that are out there,” Rimm says. “I think it’s exciting that there’s not just one, but multiple drugs that might work for a given patient. Sometimes we don’t know which one to pick – it’s an evidence-free zone. So, we need to produce that evidence and build those tests that allow you to pick between different drugs. The Troplex Assay is an example of that, and we have a couple more in the pipeline.”

Although another 30 years of the Rimm Lab isn’t likely, Rimm says he’s having too much fun to stop now.

“I think that’s the key for me. When I’m not having fun anymore, then I’ll retire. I’ve changed over the years – I’m not as intense as I used to be, and I don’t travel as much. But that’s okay. I’m still having fun. I still can get things accomplished, and, most importantly, I’m training brilliant young people.”