Photo of Leigh Ellis,  PhD

Leigh Ellis, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (716) 582-9530


leigh_ellis@dfci.harvard.edu

Leigh Ellis, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Pathology, Harvard Medical School
  • Assistant Professor of Pathology, Oncologic Pathology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

Prostate cancer (PCa) is among the most commonly diagnosed cancers in men throughout westernized countries and is a leading cause of cancer-related mortality. Hormone deprivation therapy has been the backbone for PCa treatment by inhibiting androgen receptor (AR) signaling. However, resistance to this therapy is inevitable and men will progress to castrate-resistant prostate cancer (CRPC). While most patients will undergo resistant mechanisms involving the restoration of AR signaling and maintenance of an adenocarcinoma phenotype (CRPC-Ad), an increasingly accepted mechanism of resistance in approximately a quarter of tumors involves lineage plasticity. These tumors express low to absent AR levels, often demonstrating neuroendocrine features (CRPC-NE) and are indifferent to AR signaling. Further, genomic analysis reveals that CRPC-NE evolves from CRPC-Ad, but currently the molecular mechanisms underlying CRPC-NE are not completely understood. Work within my laboratory focuses on dissecting underlying genetic/epigenetic mechanisms of progression to aggressive CRPC-NE. For this work we utilize in vitro genetically modified human and mouse cell lines, 3D organoid cultures, in vivo genetically engineered mouse models, and clinical samples coupled with innovative technology including next generation sequencing approaches. Our overall goal is to identify these novel genomic/epigenomic mechanisms which will lead to discovery of biomarkers and therapeutic targets for clinical testing.

Publications

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  • Olson BM, Gamat M, Seliski J, Sawicki T, Jeffery J, Ellis L, Drake CG, Weichert J, McNeel DG. Prostate cancer cells express more androgen receptor (AR) following androgen deprivation, improving recognition by AR-specific T cells. Cancer Immunol Res 2017. PubMed
  • Labbé DP, Sweeney CJ, Brown M, Galbo P, Rosario S, Wadosky KM, Ku SY, Sjöström M, Alshalalfa M, Erho N, Davicioni E, Karnes RJ, Schaeffer EM, Jenkins RB, Den RB, Ross AE, Bowden M, Huang Y, Gray KP, Feng FY, Spratt DE, Goodrich DW, Eng KH, Ellis L. TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup. Clin Cancer Res 2017. PubMed
  • Ku SY, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, Goodrich MM, Labbé DP, Gomez EC, Wang J, Long HW, Xu B, Brown M, Loda M, Sawyers CL, Ellis L, Goodrich DW. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 2017; 355:78-83. PubMed
  • Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen CC, Wongvipat J, Ku SY, Gao D, Cao Z, Shah N, Adams EJ, Abida W, Watson PA, Prandi D, Huang CH, de Stanchina E, Lowe SW, Ellis L, Beltran H, Rubin MA, Goodrich DW, Demichelis F, Sawyers CL. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 2017; 355:84-88. PubMed
  • Ellis L, Ku S, Li Q, Azabdaftari G, Seliski J, Olson B, Netherby CS, Tang DG, Abrams SI, Goodrich DW, Pili R. Generation of a C57BL/6 MYC-Driven Mouse Model and Cell Line of Prostate Cancer. Prostate 2016; 76:1192-202. PubMed
  • Ramakrishnan S, Ku S, Ciamporcero E, Miles KM, Attwood K, Chintala S, Shen L, Ellis L, Sotomayor P, Swetzig W, Huang R, Conroy D, Orillion A, Das G, Pili R. HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma. BMC Cancer 2016; 16:617. PubMed
  • Smonskey M, Lasorsa E, Rosario S, Kirk JS, Hernandez-Ilizaliturri FJ, Ellis L. EZH2 inhibition re-sensitizes multidrug resistant B-cell lymphomas to etoposide mediated apoptosis. Oncoscience 2016; 3:21-30. PubMed
  • Lasorsa E, Smonksey M, Kirk JS, Rosario S, Hernandez-Ilizaliturri FJ, Ellis L. Mitochondrial protection impairs BET bromodomain inhibitor-mediated cell death and provides rationale for combination therapeutic strategies. Cell Death Dis 2015; 6:e2014. PubMed
  • Ellis L, Loda M. Advanced neuroendocrine prostate tumors regress to stemness. Proc Natl Acad Sci U S A 2015; 112:14406-7. PubMed
  • Kirk JS, Schaarschuch K, Dalimov Z, Lasorsa E, Ku S, Ramakrishnan S, Hu Q, Azabdaftari G, Wang J, Pili R, Ellis L. Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer. 2015; 6:3136-46. PubMed
  • Ellis L. Determination of synthetic lethal interactions to provide therapeutic direction to end aggressive prostate cancer. Future Oncol 2015; 11:1451-4. PubMed
  • Ellis L, Lehet K, Ku S, Azabdaftari G, Pili R. Generation of a syngeneic orthotopic transplant model of prostate cancer metastasis. Oncoscience 2014; 1:609-613. PubMed
  • Ku S, Lasorsa E, Adelaiye R, Ramakrishnan S, Ellis L, Pili R. Inhibition of Hsp90 augments docetaxel therapy in castrate resistant prostate cancer. PLoS ONE 2014; 9:e103680. PubMed
  • Ellis L, Ku SY, Ramakrishnan S, Lasorsa E, Azabdaftari G, Godoy A, Pili R. Combinatorial antitumor effect of HDAC and the PI3K-Akt-mTOR pathway inhibition in a Pten defecient model of prostate cancer. 2014; 4:2225-36. PubMed
  • Ramakrishnan S, Ellis L, Pili R. Histone modifications: implications in renal cell carcinoma. Epigenomics 2013; 5:453-62. PubMed
  • Ellis L, Lehet K, Ramakrishnan S, Adelaiye R, Pili R. Development of a castrate resistant transplant tumor model of prostate cancer. Prostate 2012; 72:587-91. PubMed
  • Shen L, Ciesielski M, Ramakrishnan S, Miles KM, Ellis L, Sotomayor P, Shrikant P, Fenstermaker R, Pili R. Class I histone deacetylase inhibitor entinostat suppresses regulatory T cells and enhances immunotherapies in renal and prostate cancer models. PLoS ONE 2012; 7:e30815. PubMed
  • Ellis L, Lehet K, Ramakrishnan S, Adelaiye R, Miles KM, Wang D, Liu S, Atadja P, Carducci MA, Pili R. Concurrent HDAC and mTORC1 inhibition attenuate androgen receptor and hypoxia signaling associated with alterations in microRNA expression. PLoS ONE 2011; 6:e27178. PubMed
  • Ellis L, Pili R. Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies. Pharmaceuticals (Basel) 2011; 3:2411-2469. PubMed
  • Ellis L, Hammers H, Pili R. Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett 2009; 280:145-53. PubMed
  • Ellis L, Bots M, Lindemann RK, Bolden JE, Newbold A, Cluse LA, Scott CL, Strasser A, Atadja P, Lowe SW, Johnstone RW. The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy. Blood 2009; 114:380-93. PubMed
  • Ellis L, Atadja PW, Johnstone RW. Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther 2009; 8:1409-20. PubMed
  • Ellis L, Pan Y, Smyth GK, George DJ, McCormack C, Williams-Truax R, Mita M, Beck J, Burris H, Ryan G, Atadja P, Butterfoss D, Dugan M, Culver K, Johnstone RW, Prince HM. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma. Clin Cancer Res 2008; 14:4500-10. PubMed
  • Lindemann RK, Newbold A, Whitecross KF, Cluse LA, Frew AJ, Ellis L, Williams S, Wiegmans AP, Dear AE, Scott CL, Pellegrini M, Wei A, Richon VM, Marks PA, Lowe SW, Smyth MJ, Johnstone RW. Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proc Natl Acad Sci U S A 2007; 104:8071-6. PubMed
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