Ethan Abel


Cancers Treated:

Specializing In:

Pancreatic adenocarcinoma (pancreatic cancer) Transcription factors, Transcriptional regulation and epigenetics Signal transduction pathways in cancer Cancer stem cells Drug resistance

About Ethan Abel


Pre-graduate Research Experience

During my time in college at the State University of New York (SUNY) at Albany, I pursued a number of undergraduate research opportunities. In the summer of 2003, I was accepted into the Research for Undergraduates (REU) program, a 10-week research program run by the Wadsworth Center of the New York State Health Department. My research, under the mentorship of Dr. Ron Limberger, PhD, was examining the impact of genetic ablation of motility gene, orf4, in the spirochete bacteria Treponema denticola. During my time in the lab, I learned a number of microbiology and molecular biology techniques, including bacteria culture, RNA/DNA isolation, and quantitative reverse transcriptase PCR (qRT-PCR).

Following my participation in the REU program, I worked for two semesters in the lab of Dr. David Shub, PhD at SUNY Albany. My project entailed creating and characterizing a conditional knockout of a gene of unknown function, at the time called gene 60.1, in T4 bacteriophage. I learned a number of molecular biology techniques during this time, including gene cloning, site-directed mutagenesis, and radiolabeled DNA:DNA hybridization. My contribution to this project lead to my inclusion as a middle author in a paper published in Proceedings of the National Academy of Sciences of the United States of America.

After receiving my Bachelor’s degree in Biology in 2004, I joined the lab of Dr. Andrew Aplin, PhD at Albany Medical College as a research technician. Being a relatively new lab at the time, I was fortunate to have a great deal of research responsibility, which included helping the graduate students and postdoctoral fellow in the lab with their studies. I was also given my own exclusive project, looking at the role of focal adhesion kinase (FAK) in melanoma. During my time as a technician, I mastered a number of techniques that I would use through my graduate year. These included Western blotting, qRT-PCR, cell migration and invasion assays (scrape wound and Boyden chamber), immunofluorescence, cell culture, primary human cell isolation, flow cytometry, cell cycle/proliferation and apoptosis assays, transient and stable transfection, RNA-interference, and extensive cloning of genes and shRNAs into and packaging of lentiviral and adenoviral vectors.

Doctoral Dissertation

I received my PhD in Genetics from Thomas Jefferson University in 2012 while training in the lab of Dr. Andrew Aplin. My graduate studies focused on the stem cell and neural crest-associated transcription factor, FOXD3, which I found to be expressed in human melanoma cells. I found that FOXD3 is only expressed in melanoma cells harboring activating mutations in the kinase, BRAF, and that FOXD3 protein and mRNA levels rapidly and dramatically increase upon inhibition of the MAPK signaling cascade. I went on to demonstrate that overexpression of FOXD3 led to a potent G0/G1 arrest in melanoma, suggesting that FOXD3 might be a novel tumor suppressor. Finally, I demonstrated that this growth arrest is mediated by upregulation of p21 in a p53-dependent manner. Following publication of this study in Cancer Research in 2010, I then examined the role of FOXD3 in the response of melanoma to vemurafenib. In collaboration with fellow graduate student Kevin Basile, we found that upregulation of FOXD3 by BRAF-inhibitors protects melanoma from apoptosis (published in Oncogene in 2012). Using microarrays and ChIP-seq, I identified the neuregulin receptor, ERBB3, as a direct target of FOXD3. I demonstrated that ERBB3 expression is dependent on FOXD3, and that activation of ERBB3 promotes potent AKT signaling, protecting melanoma cells from BRAF inhibition. I found that elevated ERBB3 activation in both xenografts and in patients treated with vemurafenib, and that inhibition of ERBB3 or its partner, ERBB2, synergized with vemurafenib to block tumor growth in vivo. These results were published in The Journal of Clinical Investigation in 2013. Serving as the basis of my thesis, I concluded that FOXD3 is a transcription factor with context-dependent roles in melanoma: 1) a growth suppressor in that is actively repressed by mutant BRAF signaling and 2) a pro-survival factor when BRAF signaling is inhibited, through regulation of ERBB3. Additionally, in collaboration with fellow Aplin lab member Dr. Michele Weiss, we found that FOXD3 also transcriptionally represses the EMT transcription factor TWIST1 in melanoma cells (Molecular Cancer Research), and that TWIST1 promotes invasion of melanoma cells by upregulation of MMP1 (Cancer Research). These results highlighted the interplay between oncogenic signaling pathways and transcriptional regulation in melanoma.

Postdoctoral Research

Following my graduate studies, I became acutely fascinated by pancreatic ductal adenocarcinoma (PDA) due to its abysmal prognosis (5-year survival of 9%), its association with hyperactivation of MAPK signaling through KRAS mutations (>90% of cases), and it's poorly understood transcriptional networking. For my postdoctoral fellowship, I joined the labs of Dr. Diane Simeone in 2012 and Dr. Howard Crawford in 2017 at the University of Michigan with a goal to gain better insight into the interplay between signal transduction and transcription factors in PDA. I chose to apply this focus to understanding the biology of pancreatic cancer stem cells (PCSCs), a notoriously drug-resistant, tumor-driving subpopulation of cancer cells for which there are no effective clinical options. Initially, I focused on the role of the NOTCH pathway in maintaining the PCSC state, showing that multiple components of the NOTCH pathway are elevated in PCSCs and are critical for maintaining these cells. Targeting this pathway with clinically available γ-secretase inhibitors depletes PCSCs both alone and in combination with the conventional chemotherapeutic agent gemcitabine (Abel et al, 2014, PLoS ONE). Following this study, I identified the endodermal-lineage transcription factor HNF1A as a major regulator of the PCSC state using microarray analysis of PCSCs isolated from patient-derived PDA cells. I found that knockdown of HNF1A potently inhibits PDA cell growth, induces apoptosis, and depletes PCSCs both in vitro and in vivo (Abel et al, 2018, eLife). Additionally, ectopic expression of HNF1A increases PCSC numbers in PDA cells, while promoting cellular transformation in concert with mutant KRAS in normal pancreatic ductal cell lines. Using ChIP-seq and modified RNA-seq (Bru-seq) I found that the critical target of HNF1A is the stem cell transcription factor OCT4. Additionally, HNF1A also regulates a multitude of genes associated with poor survival in PDA. Having generated such a robust data set for HNF1A in PDA, together with so little being known about its roles, has made HNF1A a major focal point of my proposed research in my independent research career.

In addition to honing the research techniques acquired prior to my postdoctoral training, I acquired additional skills in the Simeone and Crawford labs. New skills I have acquired include working with rodents (housing, husbandry, euthanasia), subcutaneous and orthotopic (pancreas) xenotransplantation, limiting dilution assays (for measuring cancer stem cells), in vivo bioluminescent imaging, tumorsphere assays, immunohistochemistry, establishing primary cell lines (normal and cancer, human and mouse), analyzing patient data, CRISPR/Cas9-guided DNA editing/transcriptional regulation, and variant forms of RNA-seq (Bru-seq, BruChase-seq, BruUV-seq, and BruDRB-seq) to measure transcription, RNA turnover, enhancer/promoter activity, and RNA elongation rates in collaboration with Dr. Mats Ljungman (University of Michigan). Additionally, I have had the opportunity to work hands-on with bioinformatician Dr. Brian Magnuson (University of Michigan), and have become proficient in analyzing RNA-seq/ChIP-seq data.

Summary of Research Accomplishments

In addition to my 3 first author publications, I have coauthored 16 research manuscripts and 5 review articles/book chapters. I have been invited to speak at 3 research symposiums (AACR 103rd Annual Meeting 2012, American Pancreatic Association 2016 Annual Meeting, Pancreatic Cancer Action Network 2017 Annual Scientific Meeting) and have won 4 research poster awards, the JCGS Alumni Association Graduate Student Travel Fellowship (2011), and the JCGS Yun Yen MD, PhD and Sophie Yen Thesis Prize for Distinguished Research in Pathobiology (2012). I have been successful in competing for institutional and extramural funding including the Tissue Remodeling and Cardiovascular Disease training grant (T32-HL-07194) (2007-2008), the Johanna M. Nicolay Melanoma Foundation 2010 Research Scholar Award (2010-2011), and the American Cancer Society Postdoctoral Fellowship (July 2015-July 2016). Currently, I am the recipient of the Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant (August 2016-July 2021), which is a K99/R00-equilvalent grant that will help fund the first 2 years of my independent research career.

Visit the Abel Lab


Roswell Park Comprehensive Cancer Center
  • Assistant Professor of Oncology
  • Department of Molecular and Cellular Biology


Education and Training:

  • 2008-2012 - PhD - melanoma research, Genetics Graduate Program, Thomas Jefferson University, Philadelphia, PA
  • 2000-2004 - BS - Biology, State University of New York at Albany, Albany, NY


  • 2012-2019 - Postdoctoral Fellowship - pancreatic adenocarcinoma, University of Michigan, Ann Arbor, MI

Professional Memberships:

  • American Association for Cancer Research

Honors & Awards:

  • 2022 - S.A.S. Foundation for Cancer Research Grant
  • 2021 - Hirshberg Foundation for Pancreatic Cancer Research Seed Grant
  • 2016-2021 - Recipient of the Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant
  • 2015-2016 - Recipient of the American Cancer Society Postdoctoral Fellowship
  • 2012 - JCGS Yun Yen MD, PhD and Sophie Yen Thesis Prize for Distinguished Research in Pathobiology, Thomas Jefferson University, Philadelphia, PA
  • 2012 - Invited presenter in minisymposium at AACR 103rd Annual Meeting 2012-"Upregulation of ERBB3/HER3 by FOXD3, an adaptive response promoting resistance to RAF/MEK-inhibitors"
  • 2011 - International Melanoma Congress Poster Award-Best Poster on Prevention, Diagnosis, Translational Research or Treatment of Melanoma


Research Overview:

Abel Lab

I am interested in identifying and characterizing novel drivers in cancer with the goal of discovering novel therapeutic targets. The main focus of my work in recent years has been to understand the interplay between signal transduction and gene regulation (transcription and epigenetics) in human pancreatic ductal adenocarcinoma (pancreatic cancer) cells, and how this interplay drives this disease. A major thrust of my research focuses on elucidating which signaling and transcriptional pathways regulate the biological properties of pancreatic cancer stem cells, in particular, programs that control pancreatic cancer stem cell self-renewal and differentiation. Additionally, I am interested in how pancreatic cancer cells overcome oncogene ablation, in particular, ablation of mutant KRAS-signaling. Much of my research is centered on the transcription factor HNF1A, which I have identified as a novel oncogene in pancreatic cancer that drives both pancreatic cancer stem cells and resistance to KRAS ablation. I aim to uncover how HNF1A regulates these biological processes in pancreatic cancer, as well as understanding how HNF1A itself is regulated in an effort to block its function for therapeutic gain.

Lab members:

Melanie Mayberry, Ph.D. - Research Associate and Lab Manager
Bharani Muppavarapu, B.S. - Ph.D. Candidate
Katherine Crawford, B.S. - Ph.D. Candidate
Hannah Laski, B.S. - Master's Student


Full Publications list on PubMed
  • Abel EV, Goto M, Magnuson B, Abraham S, Ramanathan N, Hotaling E, Alaniz AA, Kumar-Sinha C, Dziubinski ML, Urs S, Wang L, Shi J, Waghray M, Ljungman M, Crawford HC, Simeone DM. HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties. Elife. 2018 Aug 3;7:e33947. doi: 10.7554/eLife.33947. PMID: 30074477; PMCID: PMC6122955.
  • Abel EV, Kim EJ, Wu J, Hynes M, Bednar F, Proctor E, Wang L, Dziubinski ML, Simeone DM. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer. PLoS One. 2014 Mar 19;9(3):e91983. doi: 10.1371/journal.pone.0091983. PMID: 24647545; PMCID: PMC3960140.
  • Abel EV, Simeone DM. Biology and clinical applications of pancreatic cancer stem cells. Gastroenterology. 2013 Jun;144(6):1241-8. doi: 10.1053/j.gastro.2013.01.072. PMID: 23622133.
  • Abel EV, Basile KJ, Kugel CH 3rd, Witkiewicz AK, Le K, Amaravadi RK, Karakousis GC, Xu X, Xu W, Schuchter LM, Lee JB, Ertel A, Fortina P, Aplin AE. Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J Clin Invest. 2013 May;123(5):2155-68. doi: 10.1172/JCI65780. Epub 2013 Apr 1. PMID: 23543055; PMCID: PMC3635724.
  • Abel EV, Aplin AE. FOXD3 is a mutant B-RAF-regulated inhibitor of G(1)-S progression in melanoma cells. Cancer Res. 2010 Apr 1;70(7):2891-900. doi: 10.1158/0008-5472.CAN-09-3139. Epub 2010 Mar 23. PMID: 20332228; PMCID: PMC2848900.