Staff Collaborate Conference Room

Thomas McFall, PhD

Thomas McFall, PhD

Thomas McFall, PhD

Assistant Professor


  • TBRC C4970

Contact Information

General Interests

I am interested in experimental-systems approaches that enable mechanism-based inference in genomic medicine and can help identify patients for selective therapeutic strategies.


Postdoctoral Training, The Salk Institute for Biological Studies, 2017-2020
PhD, Oncology & Cancer Biology, Wayne State University School of Medicine, Karmanos Cancer Institute, 2017
MS, Northern Michigan University, 2012
MBA, Donald W. Main School of Business, Davenport University, 2012
BS, Northern Michigan University, 2008


My primary research interests focus on longstanding problems and controversies in observed clinical scenarios which cannot not be explained in mechanistic detail. Often times evidence-based medicine can determine optimal treatment regimens for “response” vs “non-response”, yet these clinical guidelines are a result of an evolution of clinical practices and remain absent of the mechanistic underpinnings. My graduate years were focused on the role of progesterone utilizing the progesterone receptor isoform PR-A to promote invasion and metastasis. My discoveries lead to a growing field of progesterone mediated metastasis by regulating multiple pathways, not limited to but including, estrogen receptor signaling and non-coding RNA regulation. Furthermore, I addressed a longstanding controversy in the RAS signaling field, the observation that colorectal cancers harboring a G13D mutation are sensitive to EGFR inhibitors. Utilizing systems biology to explore all the known biochemical parameters of the RAS Pathway, and by employing both computational and experimental methods, I found KRAS-G13D tumors should respond to EGFR inhibition as observed in the clinic. Currently I am building a research program combining my knowledge in Systems biology, MAPK signaling, and nuclear receptor signaling to address ongoing clinical cases of extraordinary responders to better treatment strategies. Furthermore, I have formal training and experience in business strategy development, non-profit 501(c)3 business law, foundation development, and non-profit matched/for-profit collaborations.

Research Interests

Synthetic Lethality

Cancer therapy has entered a new realm where systems pharmacology is leveraged to exploit selective dependencies in tumor cells. Utilizing my training in systems pharmacology and functional screening methods, I have provided biological expertise and leadership to identify novel pharmacological inhibitors of Werner syndrome helicase (WRN) at Ideaya Biosciences as a senior scientist and biology lead. Inhibition of WRN in cancer cells that are microsatellite instability-high (MSI-H), leads to cell cycle arrest and death. Moreover, cells that are microsatellite stable (Healthy cells) are insensitive to WRN inhibition, reducing unwanted toxicity and off target effects. Creating a pharmacological inhibition of WRN helicase function represents a valuable target for cancer therapy, as 10-15 percent of cancers are MSI-H.

RAS signaling

I have focused on resolving a controversy surrounding RAS mutants conferring resistance to EGFR inhibitors. Under current guidelines, patients with an activating RAS mutation are not eligible for EGFR inhibitor therapy. In a retrospective study of clinical trial data, investigators found patients harboring a G13D mutation were sensitive to the EGFR inhibitor Cetuximab. This work has been recapitulated in both cell line and mouse models, however, absent of a detailed mechanism, the medical community has been resistant to implementing this change. We used a systems biology approach paired with experimental models to elucidate the mechanism by which G13D mutations are sensitive to EGFR inhibition. We recently published our findings in Science Signaling, Cell Communication and Signaling, Molecular & Cellular Oncology and Cell Reports. Moreover, have expanded these studies and identified 10 more RAS mutants that show sensitivity to EGFR inhibition.

MAPK signaling cross talk with apo-estrogen receptor
I have investigated a unique scenario where a patient with estrogen receptor positive (ER) ovarian cancer harboring a mutant-KRAS was resistant to MEK inhibitor and Tamoxifen, however when treatment strategy was changed to MEK inhibitor and aromatase inhibitor the patient responded with near complete ablation of the tumor. A mechanism for this finding is unknown. I have worked up a mechanism by which this phenomenon is consistent to what is observed in the basic science setting. We found phosphorylated ER is what is driving growth and is dependent upon both MAPK activation, and the estradiol-dependent ER-GPCR for signaling. This was recently accepted in The Oncologist.