Dr. GPCR Podcast

About Dr. Michael Feigin

"Dr. Michael Feigin is an Associate Professor in the Department of Pharmacology and Therapeutics, and Director of Graduate Studies of Experimental Therapeutics at Roswell Park Comprehensive Cancer Center in Buffalo, NY. He earned his Ph.D. under Dr. Craig Malbon at SUNY Stony Brook studying the role of G-protein coupled receptors (GPCRs) and their regulators in the Wnt signaling pathway. Mike then joined the lab of Dr. Senthil Muthuswamy at Cold Spring Harbor Laboratory and probed the roles of polarity proteins (Feigin, et al., Cancer Research, 2014) and GPCRs (Feigin, et al., PNAS, 2014) in breast cancer pathogenesis, using mouse models, three-dimensional cell culture and computational approaches to drug target discovery. When Dr. Muthuswamy moved to the University of Toronto, Mike joined the laboratory of Dr. David Tuveson at CSHL where he participated in the development of an organoid system for the culture of normal and malignant pancreatic tissue, allowing advances in sequencing, target discovery and biomarker development. He also continued his interest in computational analysis of cancer drivers by co-developing GECCO, an algorithm for the identification of noncoding mutations driving gene expression in pancreatic cancer (Feigin and Garvin, et al., Nature Genetics, 2017). Mike's lab has two main areas of interest: 1) alternative polyadenylation as a targetable driver of pancreatic cancer, and 2) dysregulation of the pancreatic tumor microenvironment by commonly prescribed anti-anxiety drugs."

Dr. Michael Feigin on the web

• Roswell Park

• Feigin Lab

• Google Scholar

• LinkedIn

• Twitter

• Dr. GPCR

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Quick recap

Yamina and Mike engaged in a conversation about their scientific research experiences. Mike shared his journey from his Ph.D. struggles to his current role as a professor, emphasizing the importance of resilience and creativity. They also discussed his research on cell polarity and its role in cancer progression, his work on G-protein coupled receptors (GPCRs) in breast cancer, and his interest in pancreatic cancer. The discussion also covered the challenges they face in studying GPCRs due to their low expression levels and the difficulty of localizing these receptors in tissues.

Next steps

• Mike will consider using Twitter to post job positions in his lab.

Summary

Science Roles and Resilience

Yamina and Mike had a conversation about their roles and experiences in the field of science. Yamina introduced herself and Mike shared his educational background and his journey to becoming a professor. Mike also spoke about his initial struggles during his Ph.D., such as a difficult model system and a lack of experimental results. He explained that he overcame these challenges by reading extensively and contemplating alternative plans. The conversation also highlighted the importance of resilience and creativity in scientific research.

Science Journey and Postdoc Decision

Mike discussed his journey into science and his decision to pursue a postdoc at Cold Spring Harbor. He shared that his interest in science originated from a young age and his desire to gain more knowledge about cancer biology led him to transition into using mouse models. Yamina asked about his move from in vitro to in vivo work, and Mike explained that he wanted to use better models to understand cancer signaling pathways. They also shared their personal experiences and interest in the field of biology. Towards the end, Mike mentioned that he stayed at Cold Spring Harbor even after his mentor left for Toronto.

Mike's Research on Cell Polarity and GPCRs in Cancer

Mike shared his research on cell polarity and its role in cancer progression, particularly focusing on the potential of disrupted cell polarity as a driver of tumorigenesis. He also discussed his work on G-protein coupled receptors (GPCRs) in breast cancer, identifying GPR161 as a potential drug target due to its high expression in triple negative breast cancer. Mike then transitioned to pancreatic cancer, questioning why genes are dysregulated in cancer, which led him to explore different aspects of gene regulation and its relation to cancer progression. Yamina acknowledged the difficulty in identifying GPCRs expressed in cancer cells but not in normal ones, and commended Mike's innovative approach to the question.

Career Trajectory and Faculty Position

Yamina and Mike discussed Mike's career trajectory and his decision to pursue a faculty position. Mike expressed his initial reluctance due to a lack of confidence and fear of not being ready. However, he decided to undertake another postdoc to gain more experience and confidence. He also highlighted the importance of publishing strong papers and having a clear vision for his lab. Yamina emphasized the importance of thorough preparation and planning before applying for faculty positions. They also discussed the challenges of the two-body problem, where both partners need to find suitable positions. Mike shared his strategy of developing preliminary projects and gathering data to strengthen his application.

Teamwork and Flexibility in Scientific Research

Mike shared about his recent promotion and the way he has managed his team, encouraging them to come up with their own ideas and then guiding them. Yamina congratulated Mike on his promotion and discussed the importance of flexibility in scientific research, even when starting with a clear plan. Mike also mentioned how his team collaborates closely, with weekly roundtable discussions where everyone shares their progress and issues. The conversation ended with Yamina expressing interest in learning more about Mike's two main research areas in his lab.

GPCR Targeted Drugs and Gene Regulation in Cancer Cells

Mike presented research on the effect of GPCR-targeted drugs on cancer-associated fibroblasts and discussed their work on gene regulation in fibroblasts. He highlighted their interest in non-coding mutations in promoters and the 3'UTR region important for gene regulation. Mike also shared about a drug that targets an enzyme involved in mRNA cleaving, which has been found to stop cancer cells from growing and invading. He also discussed the impact of disrupting histone processing on rapidly proliferating cells, such as cancer cells, and suggested a therapeutic index for a drug called JTE-6.7. Yamina asked about the typical role of the enzyme and the challenges in delivering a molecule to target this enzyme and only cancer cells.

Cytokine Inhibition, Collaboration, and Anti-Anxiety Drug Research

Mike discussed the ongoing research on a drug that inhibits cytokine synthesis, its potential in killing cancer cells, and the team's efforts to understand its resistance mechanisms. He also touched upon a collaboration with Todd Ricky's group at UPenn to explore the GPCR side of the lab, which led to the discovery of potential tumor suppressors and oncogenes in melanoma. Furthermore, Mike mentioned a qualifying exam where students proposed new projects, highlighting Abby Cornwell's project on the effects of anti-anxiety drugs on pancreatic cancer patients, and the team's research on the potential issues with certain anti-anxiety drugs. The team found that these drugs could interact with GPR68, which is highly expressed in cancer-associated fibroblasts and is crucial for their function, leading to complications in cancer patients. The team is now examining other anti-anxiety drugs and common patient medications in the context of pancreatic cancer.

GPCRs and Cancer Immune Modulation

Yamina and Mike had a discussion about their research on GPCRs, specifically focusing on GPR68 and its role in the tumor microenvironment. They also touched upon the potential of GPCR modulation in stimulating the immune system to fight cancer. Mike shared his team's current focus on alprazolam, an anti-anxiety medication that has unexpected effects in the tumor microenvironment. They also discussed the challenges they face in studying GPCRs due to their low expression levels and the difficulty of localizing these receptors in tissues. Mike expressed a need for better tools to study GPCR localization in tissues.

Scientific Journey and Drug Discovery Challenges

Mike shared significant moments in his scientific journey, including the discovery of RGS proteins and its impact on his research approach. He also discussed his experiments and discoveries about GPR161 in mammary epithelial cells, the effect of alprazolam on tumors, and the potential dangers of drug interactions. Yamina proposed further exploration of dosage and length of treatment in a mouse model and suggested using a biosensor-based assay to examine dose-response curves. The conversation highlighted the complexities and challenges of drug prescription and the potential for alternative treatments.

Science Journeys and Career Advice

Yamina and Mike discussed their experiences in the field of science. Mike advised junior scientists to focus on projects they are passionate about, emphasizing that ownership and full investment in a project can make dealing with challenges easier. Yamina shared her personal journey, describing how she took her project in a different direction and felt a sense of ownership. Mike reflected on his early years as a postdoc, admitting that he lacked focus and didn't see the direct impact of his work on patients. He highlighted the importance of re-evaluating one's work and its potential implications. Towards the end, Yamina asked about job opportunities in Mike's lab, to which Mike responded that potential candidates can find him on Twitter.