Joshua F. Zeidner

MD, Assistant Professor, UNC-Chapel Hill, Clinical Research

MD
Assistant Professor
UNC-Chapel Hill
Clinical Research

Area of interest

My research interests include discovering innovative methods to improve outcomes, drug discovery and development, and designing clinical trials in acute myeloid leukemia (AML)  myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). I lead the Leukemia Clinical Trials Research Protocol Office Disease (POD) Group where we have a multitude of cutting-edge clinical trials for acute leukemia, MDS, and MPNs. I am the Principal Investigator of industry-sponsored, investigator-initiated, and academic collaborative clinical trials evaluating novel agents in MDS and AML. My research focus encompasses drug development in two distinct pathways in AML: 1) cyclin-dependent kinase inhibitors, and 2) innovative immunotherapeutic strategies.
Cyclin-Dependent Kinase Inhibitors:
Under the mentorship of Drs. Judy Karp and B. Douglas Smith, I was the lead investigator and author on a randomized phase 2 study of a novel cyclin-dependent kinase-9 (CDK9) inhibitor, Alvocidib, followed by cytarabine and mitoxantrone (FLAM) versus standard-of-care 7+3 in newly diagnosed AML patients. 7+3 has been traditionally considered ‘standard’ induction therapy for newly diagnosed AML for the past 4 decades despite suboptimal outcomes. We found that FLAM led to a significant improvement in overall response. In collaboration with Tolero Pharmaceuticals, we are interested in assessing predictive biomarkers of response to Alvocidib. Due to its potent inhibition of CDK9, Alvocidib inhibits and down-regulates MCL-1, a critical pro-survival gene in AML. We hypothesize that patients dependent on MCL-1 for leukemia survival may respond best to Alvocidib. To that end, I am the lead Principal Investigator of 3 clinical trials assessing the role of Alvocidib in newly diagnosed and relapsed/refractory AML patients.
Innovative Immunotherapy Approaches:
  1. Immunomodulation of T cells- In collaboration with Drs. Gojo and Luznik at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, I am the Co-Principal Investigator of a phase I study of an immunomodulatory agent (IMiD), pomalidomide, during early lymphocyte recovery after induction chemomtherapy as a means to augment an anti-leukemic immune response after chemotherapy. We found that pomalidomide is safe, has clinical activity after induction chemotherapy, and leads to effective T cell modulation. We aim to expand this immunomodulatory platform at early lymphocyte recovery to other treatment settings in AML.
  2. Checkpoint Inhibition- I am the lead PI of a multicenter phase II study of high dose cytarabine followed by pembrolizumab, a monoclonal antibody targeting PD-1, in relapsed/refractory AML. In collaboration with Drs. Jonathan Serody and Benjamin Vincent (UNC) and Leo Luznik and Ivana Gojo (Johns Hopkins), our goal is to assess for predictive immune biomarkers of response to pembrolizumab in AML in order to better tailor checkpoint inhibitors for subsets of AML patients who are most likely to respond.

Awards and Honors

  • 2016 Junior Faculty Development Award
  • 2014 Leukemia and Lymphoma Society Special Fellow in Clinical Research
  • 2014 Bradley Stuart Beller Merit Award- awarded top abstract submitted by fellow to 2014 ASCO Conference
  • 2013 Recipient of National Institute of Health (NIH) Loan Repayment Program
  • 2013 ASCO Conquer Cancer Foundation Young Investigator Award, In memory of John R. Durant, MD
  • 2012 American Society of Hematology (ASH) Abstract Achievement Award for 2012 ASH Conference, Atlanta, GA
  • 2012 Selected Participant in AACR/ASCO Methods in Clinical Cancer Research Workshop, Vail, CO
  • 2012 Samuel Smith Leukemia Fellowship Award
  • 2008 Department of Medicine Academic Award
  • 2007 Selected Participant for Ninth Annual American College of Physicians Board Review
  • 2007 Alpha Omega Alpha Medical Honor Society
  • 2006 American Society for Clinical Pathology Award
  • 2004 Magna Cum Laude
  • 2002 Golden Key International Honor Society
  • 2000 Dean’s Scholarship

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