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Ashkan Emadi, MD, PhD

Academic Title:

Professor

Primary Appointment:

Medicine

Secondary Appointment(s):

Pharmacology

Administrative Title:

Program Director of the Hematology-Medical Oncology Fellowship Program

Additional Title:

Associate Director for Clinical Research, University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC)

Location:

UMMC, N9E24

Phone (Primary):

(410) 328-6841

Fax:

(410) 328-2578

Education and Training

M.D., Tehran University of Medical Sciences

Ph.D., Organic Chemistry, Illinois Institute of Technology, Chicago, IL

Intern, Internal Medicine, University of Kentucky, Lexington, KY

Resident, Internal medicine, University of Cincinnati, Cincinnati, OH

Fellowship, Hematology / Medical Oncology, Johns Hopkins University, Baltimore, MD

Biosketch

Dr. Emadi is a hematologist/medical oncologist and an organic chemist who is a Professor of Medicine and Pharmacology at the University of Maryland School Of Medicine, and Marlene & Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). He had served as a medical officer at the Division of Hematology Products (DHP), Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research (CDER), United States Food and Drug Administration (FDA).

Dr. Emadi has been working on changing the outcomes for acute leukemias in adults by designing, conducting and analyzing rationally-based innovative strategies that will positively affect cures and translate into prolongation of meaningful survival. His in-depth knowledge and experience in organic chemistry and drug design, preclinical and clinical development, and drug approval covers the entire spectrum of drug development.

Dr. Emadi developed novel methodologies for the regiospecific synthesis of multiple naphthoquinone derivatives related to the natural product conocurvone, which exhibit HIV integrase inhibitory activity as well as anti-neoplastic activity. He was granted “Highest Standards of Academic Achievement Award” for his scholarly activity during Ph.D. He holds two patents on the compounds, their synthesis and their biologic activity entitled "Anti-Retroviral Multi-Quinone Compounds and Regiospecific Synthesis Thereof" and "Aziridinyl dimeric naphthoquinone, new potent anti-neoplastic agents with novel mechanisms of action". He was awarded the prestigious “Martin and Mary Kilpatrick Award” for exceptional ability and promise in chemistry and outstanding achievement in chemical research.

Dr. Emadi's clinical translational research is focused on exploiting and targeting glutamine and glucose metabolic pathways in neoplastic cells. Dr. Emadi is the Principal Investigator of fully funded investigator-initiated clinical trials for treatment of patients with newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) involving tryptophan and glutamine metabolisms. He is particularly interested in exploiting immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) and asparaginase-induced glutamine depletion combination therapy for AML treatment. 

The discovery of isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations has triggered intensive efforts to develop novel targeted therapies against these mutations in different neoplasms. The first IDH2 inhibitor was approved for treatment of patients with relapsed or refractory AML in 2017 and there are several IDH1/2 inhibitors are currently under early phase clinical investigation. In the last decade, Dr. Emadi's approach to targeting these mutations has been unique and different from mainstream drug development efforts. Instead of directly inhibiting mutant enzymes, he has been investigating targeting the proteomic, metabolic, genetic and epigenetic consequences of these mutations such as glutamine addiction, BRCAness, and aberrant DNA hypermethylation.

Fianlly, Dr. Emadi is dedicated to mentoring the next generation of basic and clinical investigators who will build upon and refine any inroads that the current generation of cancer investigators makes in overcoming these devastating diseases. To this end, at UMGCCC, Dr. Emadi serves as Director of the three-year Accreditation Council for Graduate Medical Education (ACGME)-accredited Hematology and Oncology Fellowship Program. He annually recruits and mentors six of the best candidates who are board eligible in internal medicine and wish to achieve training and certification in both hematology and medical oncology.

Research/Clinical Keywords

Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Myelodysplastic Syndromes (MDS), Myeloproliferative Neoplasms (MPN)

Highlighted Publications

Clinical Translational Investigations on Leukemia:

Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: Golden anniversary. Nature Reviews Clinical Oncology. 2009; 6(11): 638-647.

Emadi A, Karp JE. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia. Pharmacogenomics. 2012; 13(11):1257-1269.

Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV. Inhibition of glutaminase selectively suppresses the growth of primary AML cells with IDH mutations. Experimental Hematology. 2014; 42(4): 247-251.

Emadi A, Zokaee H, Sausville EA. Asparaginase in the Treatment of Non-ALL Hematologic malignancies. Cancer Chemotherapy and Pharmacology. 2014; 73(5):875-883.

Sammons SL, Pratz KW, Smith BD, Karp JE, Emadi A. Sorafenib is tolerable and improves clinical outcomes in patients with FLT3-ITD acute myeloid leukemia prior to stem cell transplant, and after relapse post-transplant. American Journal of Hematology. 2014; 89(9):936-938.

Oliver N, Short B, Thein M, Duong VH, Tidwell ML, Sausville EA, Baer MR, Kamangar F, Emadi A. Treatment of Catheter-related Deep Vein Thrombosis in Acute Leukemia Patients with Anticoagulation. Leukemia & Lymphoma. 2015; 56(7):2082-2086.

Emadi A, Faramand R, Carter-Cooper B, Tolu S, Ford LA, Lapidus RG, Wetzler M, Wang ES, Etemadi A, Griffiths EA. Presence of isocitrate dehydrogenase (IDH) mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia (AML). American Journal of Hematology. 2015; 90(5):E77-79.

Emadi A, Sadowska M, Carter-Cooper B, Bhatnagar V, van der Merwe I, Levis MJ, Sausville EA, Lapidus RG. Perturbation of cellular oxidative state induced by dichloroacetate and arsenic trioxide for treatment of acute myeloid leukemia. Leukemia Research. 2015; 39(7):719-729.

Fathi AT, Wander SA, Faramand R, Emadi A. Biochemical, epigenetic, and metabolic approaches to target IDH mutations in acute myeloid leukemia. Seminars in Hematology. 2015; 52(3):165-171.

Etemadi A, Kamangar F, Islami F, Poustchi H, Pourshams A, Brennan P, Boffetta P, Malekzadeh R, Dawsey SM, Abnet CC, Emadi A. Mortality and cancer in relation to ABO blood group phenotypes in the Golestan Cohort Study. BMC Medicine. 2015;13(1):8.

Emadi A. Exploiting AML Vulnerability: Glutamine Dependency. Blood. 2015; 126(11):1269-1270.

Babakoohi S, Lapidus RG, Faramand R, Sausville EA, Emadi A. Comparative analysis of methods for detecting isocitrate dehydrogenase 1 and 2 mutations and their metabolic consequence, 2-hydroxyglutarate, in different neoplasms. Applied Immunohistochemistry & Molecular Morphology.2016 March 3, [Epub ahead of print].

Reddy H, Duffy A, Holtzman NG, Emadi A. The role of β-elimination for the clinical activity of hypomethylating agents and cyclophosphamide analogues. American Journal of Cancer Therapy and Pharmacology. 2016; 3(1):1-8.

Emadi A, Bade NA, Stevenson B, Singh Z. Minimally-myelosuppressive asparaginase-containing induction regimen for treatment of a Jehovah’s Witness with mutant IDH1/NPM1/NRAS acute myeloid leukemia. Pharmaceuticals (Basel). 2016; 9(1), 12; doi:10.3390/ph9010012.

Ding J, Karp JE, Emadi A. Elevated Lactate Dehydrogenase (LDH) Can be A Marker of Immune Suppression in Cancer Cells: Interplay Between Hematologic and Solid Neoplastic Clones and Their Microenvironment. Cancer Biomarkers. 2017; 19(4):353-363.

Emadi A, Lapidus RG. Breaking mitochondrial fasting for cancer treatment: Old wine in new bottles. Journal National Cancer Institute. 2017; 109 (11):djx069.

El Chaer F, Holtzman NG, Binder E, Porter NC, Singh ZN, KokaM, Rapoport AP, Emadi A. Durable Remission with Salvage Decitabine and Donor Lymphocyte Infusion (DLI) for Relapsed Early T-Cell Precursor Acute Lymphoblastic Leukemia (T-ALL). Bone Marrow Transplantation. 2017; 52(11):1583-1584.

McCusker MG, El Chaer F, Duffy A, Emadi A, Duong VH. Combination of blinatumomab and vincristine sulfate liposome injection for treatment of relapsed Philadelphia chromosome positive B-cell acute lymphoblastic leukemia. American Journal of Leukemia Research, 2018; 2(1):1-4.

Emadi A, Law JY, Strovel ET, Lapidus RG, Jeng LJB, Lee M, Blitzer MG, Carter-Cooper BA, Sewell D, Van Der Mewre I, Philips S, Imran M, Yu SL, Li H, Amrein PC, Duong VH, Sausville EA, Baer MR, Fathi AT, Singh ZN, Bentzen AM. Asparaginase Erwinia Chrysanthemi Effectively Depletes Plasma Glutamine in Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia. Cancer Chemotherapy and Pharmacology. 2018; 81(1):217-222.

Design and Synthesis of Naphthoquinone Chemotherapeutics:

Emadi A, Harwood JS, Kohanim S, Stagliano KW. Regiocontrolled Synthesis of the Trimeric Quinone Framework of Conocurvone. Organic Letters. 2002; 4(4): 521-524.

Stagliano KW, Emadi A. Anti-Retroviral Multi-Quinone Compounds and Regiospecific Synthesis Thereof. United States Patent and Trademark Office; The US Patent Number 6828347; December 07, 2004.

Stagliano KW, Emadi A, Lu Z, Malinakova HC, Twenter B, Yu M, Holland LE, Rom AM, Harwood JS, Amin R, Johnson AA, Pommier Y. Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone. Bioorganic and Medicinal Chemistry. 2006; 14(16): 5651-5665.

Emadi A, Ross AE, Cowan KM, Fortenberry YM, Vuica-Ross M. A Chemical Genetic Screen for Modulators of Asymmetrical 2,2´-Dimeric Naphthoquinone Cytotoxicity in Yeast. PLoS One. 2010; 5(5):e10846.

Emadi A, Le A, Harwood CA, Stagliano KW, Kamangar F, Ross AE, Cooper CR, Dang CV, Karp JE, Vuica-Ross M.  Metabolic and Electrochemical Mechanisms of Dimeric Naphthoquinones Cytotoxicity in Breast Cancer Cells. Bioorganic and Medicinal Chemistry. 2011; 19(23): 7057-7062.

Mukhi Pidugu LS, Mbimba JCE, Ahmad M, Pozharski E, Sausville EA, Emadi A, Toth EA. A direct interaction between NQO1 and a chemotherapeutic dimeric naphthoquinone. BMC Structural Biology. 2016; 16(1):1-10.

Lapidus RG, Carter-Cooper BA, Sadowska M, Choi EY, Wonodi O, Muvarak N, Natarajan K, Mukhi Pidugu LS, Jaiswal AK, Toth EA, Rassool FV, Etemadi A, Sausville EA, Baer MR, Emadi A. Hydroxylated dimeric naphthoquinones increase generation of reactive oxygen species, induce apoptosis of AML cells and are not substrates of the multidrug resistance proteins. Pharmaceuticals (Basel). 2016; 9(1), 4.

Carter-Cooper BA, Fletcher S, Ferraris D, Choi EY, Kronfli D, Dash S, Truong P, Sausville EA, Lapidus RG, Emadi A. Synthesis, characterization and antineoplastic activity of bis-aziridinyl dimeric naphthoquinone - A novel class of compounds with potent activity against acute myeloid leukemia cells. Bioorganic & Medicinal Chemistry Letters. 2016 Nov 17. [Epub ahead of print]

Additional Publication Citations

Emadi A, Karp JE. Acute Leukemia: An Illustrated Guide to Diagnosis and Treatment. Demos Medical Publishing, New York, NY, 2017 (Available July 26th, 2017), 368 pages; ISBN: 9781620701003, ebook ISBN: 9781617052774, Image Bank ISBN: 9780826172686, LCCN: 2016055279, Copyright© 2018 Springer Publishing Company. The book contains over 40 tables and over 220 illustrations.

The book provides a unique, comprehensive and concise visual reference on AML and ALL seen in children and adults

This book addresses all aspects of AML and ALL including their epidemiology, risk factors, cytogenetics and mutational characteristics, diagnoses, clinical management and prognoses which are imperative and challenging for medical students, residents, hematology and medical oncology fellows, and even community oncologists and hematologists. provides helpful and evidence-based treatment recommendations when providing induction therapy, consolidation therapy, and bone marrow transplantation

It presents complex information relying predominantly on pictorial depictions rather than traditional text in a visually instructive format, and replaces the wordiness of a traditional textbook with original and adapted illustrations, instructive schemata and diagrams, photomicrographs, tables, detailed figure legends, and practical, “bite-sized” text.

Research Interests

Tumor Metabolism: Targeting Glutamine Metabolism in AML with Asparaginase Combination Therapy

Targeted Therapy: Overcoming Resistance to FLT3 Inhibitors

Cancer Immunotherapy: Bi-specific T-cell engagers (BiTEs) in ALL and AML, Targeting IDO Pathway in AML