Ashkan Emadi, MD, PhD

Alexander Bland Osborn Endowed Chair and Distinguished Professor of Medical Oncology

Organization:

West Virginia University WVU Cancer Institute

Department:

Department of Medical Oncology

Classification:

Faculty

• MD, Tehran University of Medical Sciences, 1996
• PhD, Illinois Institute of Technology, 2004
• MD, University of Kentucky School of Medicine, 2005
• MD, University of Cincinnati, School of Medicine, 2007
• MD, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, 2010

Contributions to Science

1. Discovery of novel methodologies for the regiospecific synthesis of oligomeric naphthoquinones. Dr. Emadi was the first to use hydroxyquinone anions in the stepwise substitution reactions to form quinone-quinone bonds. This process utilizes inexpensive and readily available materials to synthesize large scale dimeric and trimeric naphthoquinones. This synthetic route forms a chemical bond between two SP² carbons in quinone systems through a stepwise replacement of the halogens in 2,3-dihalonaphthoquinones by hydroxyquinone as an active methylene. This method has been successfully used and multiply cited by organic and medicinal chemists worldwide to synthesize medicinal oligomeric quinones.
   a. Emadi A, Harwood JS, Kohanim S, Stagliano KW. Regiocontrolled synthesis of the trimeric quinone framework of conocurvone. Org Lett. 2002 Feb 21;4(4):521–4.
   b. Stagliano KW, Emadi A, Lu Z, Malinakova HC, Twenter B, et al. Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone. Bioorg Med Chem. 2006 Aug 15;14(16):5651–65.
   c. Stagliano KW, Emadi A. Anti-retroviral multi-quinone compounds and regiospecific synthesis thereof. United States patent 6,828,347. 2004 Dec 7.
   d. 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 May 26;5(5):e10846. PubMed PMID: 20520766.

2. Antineoplastic activity of dimeric naphthoquinone. Dr. Emadi and his colleagues discovered that halogenated, aziridinyl, and hydroxyethyl amine dimeric naphthoquinones (BiQs) are active against malignant cells including acute myeloid leukemia (AML), breast cancer, and prostate cancers with remarkable potency and selectivity. BiQs exert their anticancer activities through targeting mitochondrial respiration and cellular redox states, alkylating DNA, and inhibiting NQO1.
   a. Emadi A, Le A, Harwood CA, Stagliano KW, Kamangar F, et al. Metabolic and electrochemical mechanisms of dimeric naphthoquinones cytotoxicity in breast cancer cells. Bioorg Med Chem. 2011 Dec 1;19(23):7057–7062.
   b. 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 Jan 19;9(1).
   c. 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. Bioorg Med Chem Lett. 2017 Jan; 27(1):6–10.
   d. Ferraris D, Lapidus R, Truong P, Bollino D, Carter-Cooper B, Lee M, Chang E, LaRossa-Garcia M, Dash S, Gartenhaus R, Choi EY, Kipe O, Lam V, Mason K, Palmer R, Williams E, Ambulos N, Kamangar F, Zhang Y, Kapadia B, Jing Y, Emadi A. Pre-Clinical Activity of Amino-Alcohol Dimeric Naphthoquinones as Potential Therapeutics for Acute Myeloid Leukemia. Anticancer Agents Med Chem. 2022;22(2):239-253. 

3. Exploiting glutamine metabolic pathways for cancer treatment. Dr. has used the glutaminase activity of clinical asparaginases (both E. coli and Erwinia chrysanthemi [Crisantaspase]) to effectively deplete glutamine and investigate its effect on and eIF4E-4EBP1 interaction on cap binding complex and inhibition of cap-dependent translation. For the first time, Dr. Emadi and his team reported that crisantaspase resulted in complete plasma glutamine depletion in patients and was associated with antileukemic activity in relapsed/refractory AML with no dose-limiting toxicity.
   a. Emadi A, Law JY, Strovel ET, Lapidus RG, Jeng LJB, et al. Asparaginase Erwinia Chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed or refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2018 Jan;81(1):217-222.
   b. Emadi A, Kapadia B, Bollino D, Bhandary B, Baer MR, Niyongere S, Strovel ET, Kaizer H, Chang E, Choi EY, Ma X, Tighe KM, Carter-Cooper B, Moses BS, Civin CI, Mahurkar A, Shetty AC, Gartenhaus RB, Kamangar F, Lapidus RG. Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia. Leukemia. 2021 Jul;35(7):1907-1924.
   c. Kapadia B, Shetty AC, Bollino D, Bhandary B, Lapidus RG, Mahmood K, Mahurkar A, Gartenhaus RB, Eckert RL, Emadi A. Translatome changes in acute myeloid leukemia cells post-exposure to pegcrisantaspase and venetoclax. Exp Hematol. 2022 Apr;108:55-63.
   d. Emadi A, Lapidus RG. Asparaginase-induced Glutamine Depletion Combined with BCL-2 Inhibition for Treatment of Hematologic and Solid Cancers. UMB Docket No: AE-2019-063; PCT No. PCT/US2019/067374, PCT Filed 12/19/2019; USPTO Application No. 17/415,344, Filing Date 06/17/2021. Publication No. US-2022-0054606-A1, Publication Date 02/24/2022.

4. Investigator-initiated clinical trials targeting amino acid metabolisms for treatment of acute myeloid and lymphoblastic leukemias (AML & ALL).
   a. An Open-Label, Single-Arm Pharmacokinetic Study of Intravenous Erwinaze (asparaginase Erwinia chrysanthemi) for the Treatment of Adult Patients with Acute Myeloid Leukemia (AML) with or without Isocitrate Dehydrogenase (IDH) Mutations (GCCC1336, IND 121263), NCT02283190.
   b. Phase 1b / Randomized Phase 2a Trial of Indoximod in Combination with Idarubicin and Cytarabine in Patients with Newly Diagnosed AML (GCCC1562, IND 127155), NCT02835729.
   c. Pegcrisantaspase in Combination with Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia (GCCC2087, IND 154601), NCT04666649.
   d. A Phase 1 Trial of Calaspargase Pegol-mknl in Combination with High Dose Cytarabine and Idarubicin in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (GCCC2157, IND 157111), NCT04953780.

2003       Martin and Mary Kilpatrick Award, Illinois Institute of Technology, Department of Biological, Chemical and Physical Sciences; awarded $30,000 for exceptional ability and promise in chemistry and outstanding achievement in chemical research
2004       Letter of Honor, Illinois Institute of Technology; awarded by Dean of the Graduate College for recognition of The Highest Standards of Academic Achievement
2006       The First Place Poster Presentation Award, University of Cincinnati College of Medicine, Department of Medicine; awarded for the best   clinical vignette (residency)
2008-2010  T32 Training Program in Hematology (5T32HL007525), Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center
2008       Training Award, Molecular Biology in Clinical Oncology Workshop, American Association for Cancer Research, Aspen, CO
2009       Travel Award, 4^th Biennial Workshop on the Clinical Translation of Epigenetics in Cancer Therapy, Coral Gables, FL
2009       Excellence in Translational Research Award, Johns Hopkins University, School of Medicine, Department of Pathology; awarded for translational research in targeting mitochondrial pathways for cancer treatment
2009       Research Training Award for Fellows, American Society of Hematology; one of the top ten finalists
2010       Research Training Award for Fellows, American Society of Hematology; awarded $50,000 for one year salary support for the research project “Targeting tumor metabolism for the treatment of lymphoma and leukemia”
2013       Faculty Teacher of The Year Award, UMSOM, Department of Medicine; awarded for the faculty member in the Division of Hematology/Oncology who has demonstrated excellence in teaching as chosen by the faculty and fellows
2015       Outstanding Faculty Mentor Award, UMSOM, Department of Medicine; awarded in recognition of exemplary research and clinical mentorship
2017       Faculty Teacher of The Year Award, UMSOM, Department of Medicine; awarded for the faculty member in the Division of Hematology/Oncology who has demonstrated excellence in teaching as chosen by the faculty and fellows
2018       Preceptor Recognition Award, UMSOM; awarded for the exceptional dedication, mentorship, and commitment to the students of University of Maryland School of Medicine and the outstanding contributions to the Introduction to Clinical Medicine II course

Books

1. Ashkan Emadi , Judith E. Karp. Acute Leukemia: An Illustrated Guide to Diagnosis and Treatment. Demos Medical Publishing, New York, NY, 2017, 368 pages; ISBN: 9781620701003, ebook ISBN: 9781617052774, Image Bank ISBN: 9780826172686, LCCN: 2016055279, Copyright^© 2018 Springer Publishing Company.
2. Ashkan Emadi, Judith E. Karp. Cancer Pharmacology: An Illustrated Manual of Anticancer Drugs. Demos Medical Publishing, New York, NY, 2019, 312 pages; ISBN 13: 9780826162038, EISBN: 9780826162045
3. Ashkan Emadi, Judith E. Karp. Cancer Pharmacology: An Illustrated Manual of Anticancer Drugs. Second Edition. Demos Medical Publishing, New York, NY, 2023; ISBN: 0826149324, ISBN13: 9780826149329. 
4. Ashkan Emadi, Jennie Y. Law. Leukemias. The Merck Manual of Diagnosis and Therapy, 20^th Edition Wiley, 2018. Last full review/revision May 2020.

• Overview of Leukemia: https://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/overview-of-leukemia?query=leukemia
• Acute Myeloid Leukemia (AML): https://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/acute-myeloid-leukemia-aml
• Acute Lymphoblastic Leukemia (ALL): https://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/acute-lymphoblastic-leukemia-all
• Chronic Myeloid Leukemia (CML): https://www.merckmanuals.com/en-ca/professional/hematology-and-oncology/leukemias/chronic-myeloid-leukemia-cml
• Chronic Lymphocytic Leukemia (CLL): https://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/chronic-lymphocytic-leukemia-cll
• Myelodysplastic Syndrome (MDS): https://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/myelodysplastic-syndrome-mds
• Consumer chapter: https://www.merckmanuals.com/home/blood-disorders/leukemias/overview-of-leukemia?query=leukemia

The chapters were viewed 505,784 times worldwide in 2020.  The chapters were viewed 2,203,834 times worldwide in 2023.

Ashkan Emadi, MD, PhD, is the inaugural endowed chairman of the Department of Medical Oncology at the WVU School of Medicine. He’s also the Alexander Boland Osborn Distinguished Professor of Medical Oncology. He serves as physician-in-chief for Medical Oncology and associate center director for Translational Research at the WVU Cancer Institute.

Dr. Emadi is dedicated to building an academic and clinical department and team that provides state-of-the-art cancer care, inclusive of investigative programs, to the diverse population served by the WVU Cancer Institute. He is also focused on improving access for underserved communities.

With a PhD in organic chemistry, Dr. Emadi has pioneered methodologies for synthesizing compounds with potent anti-HIV and anti-cancer activities. In his lab, Dr. Emadi directs cutting-edge research combining an intimate knowledge of the cellular pathways he is targeting with a complete familiarity and deep commitment to the patients he is treating. Dr. Emadi is a world-renowned scientist in targeting glutamine metabolism and dependency in acute myeloid leukemia, pancreatic adenocarcinoma, mesothelioma, and brain tumors, including both isocitrate dehydrogenase (IDH) mutant astrocytoma and IDH wild type glioblastoma. He has designed and conducted several novel state-of-the-art clinical trials focusing on amino acid metabolism in cancer.

Nationally and internationally, Dr. Emadi is among a very select group of oncology physician-scientists who possesses comprehensive knowledge and hands-on experience in all stages of cancer drug discovery, from chemical synthesis and in vitro and in vivo studies to all phases of clinical trials, and drug approval by regulatory agencies.

Over the course of his career, Dr. Emadi has been the author, co-author, or editor of nearly 200 research articles, presentations in national and international scientific meetings, book chapters, and three novel fully illustrated books, including a unique Cancer Pharmacology textbook. His work has been published in top tier journals, such as New England Journal of Medicine, Blood, Leukemia, American Journal of Hematology, British Journal of Haematology, and JAMA.

Dr. Emadi is an exceptional teacher. He has been a great mentor for physicians and basic scientists at all stages of training and has been recognized consistently throughout his career. Training the next generation of scientists is one of his life missions. To date, he has spent several hundred hours on personalized direct mentoring of nearly 40 college students, interns, PhD and medical students, internal medicine residents, and Hematology/Oncology fellows and junior faculty. He is proud that the vast majority of his mentees are now thriving academic investigators, teachers, and clinician-scientists all around the United States.

Dr. Emadi is a devoted basic/translational researcher.

In his lab (https://emadicancerlab.com), Dr. Emadi directs cutting-edge preclinical research focused on exploiting the amino acid metabolism of hematologic and epithelial and mesenchymal cancer cells. His group is one of the world leaders on targeting glutamine metabolism and dependency in acute myeloid leukemia (AML), pancreatic adenocarcinoma, mesothelioma, brain tumors including both isocitrate dehydrogenase (IDH) mutant astrocytoma and IDH wild type glioblastoma.

Dr. Emadi has had several grants and patents on asparaginase combination therapy for blood cancers and solid tumors investigating mechanistically driven synergism between glutamine depletion and other chemotherapeutics as well as the effect on global mRNA translation in cancer cells. He has designed and conducted several novel state-of-the-arts clinical trials (NCT02283190, NCT04666649, NCT04953780, NCT02835729, NCT04827745). Dr. Emadi was the first to report that in patients with AML, plasma glutamine can safely be depleted to an undetectable level with promising antileukemic effect.

As a recent example of his work, Dr. Emadi and his team translated their preclinical discovery of venetoclax (Ven) and pegcrisantaspase (PegC) as a novel, well-tolerated and highly active regimen in vivo for the treatment of AML with complex karyotypes into an investigator-initiated clinical trial (NCT04666649). The mechanism of action of VenPegC combination is completely unique to the field that could overcome Ven resistance in AML by inhibition of cap-dependent mRNA translation through increasing the inhibitory interaction between 4EBP1 and its substrate eIF4E resulting in decreased expression of protein involved in Ven-resistance such as Mcl1. VenPegC is tolerable at maximum tolerated dose and did not cause venous thromboembolism, hemorrhage, hepatic failure, pancreatitis, or hypersensitivity reactions. VenPegC induced approximately 35% complete remission in heavily pretreated AML patients even with prior exposure to Ven; majority of these patients had limited or no therapeutic options. This treatment is entirely feasible to deliver in outpatient setting and oncologists treating patients with leukemia are quite familiar with their administration, with their therapeutic potential and their potential toxicities.

See attached CV

Medical Specialties

• Cancer / Oncology

Board Certifications

• Hematology, American Board of Internal Medicine
• Medical Oncology, American Board of Internal Medicine

Special Training

• Fellowship, Medical Oncology and Hematology
  Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, 2010
• Residency, Resident, Internal Medicine
  University of Cincinnati, 2007
• Residency, Internship, Internal Medicine
  University of Kentucky, 2005

As a board-certified hematologist & medical oncologist, through his time attending on inpatient Hematologic Malignancies/Transplantation and Cellular Therapy service and outpatient clinic, Dr. Emadi is completely involved in the care of his patients and their families. In his clinical role, he has been combining an intimate knowledge of the pathways he is targeting with a complete familiarity with the patients he is treating. Dr. Emadi puts his patients first in everything he does. He always prioritize patients and their loved ones. 

Here are a few patient testimonial examples (upon leaving Maryland and coming to West Virginia):

"Dr. Emadi, My heart is broken that you are leaving and will no longer be taking care of me. You have meant the world to me these past years. I have great love in my heart for you and the care you have provided me. I will miss you very much. Above my own feelings and sense of loss, I wish you health, happiness and every future success. God bless you for your dedication and commitment to the medical science, and most importantly, the hope and confidence to face an uncertain future you give to your patients. I will never forget you and what you have done for me. Thank you. JS"

"Dr. Emadi, I don't know if this will get to you before you leave, but I wanted to thank you again for everything you have done for me. YOU SAVED MY LIFE!! I will be forever grateful and indebted to you! You are a medical professional that one can only hope to be under when medical care is needed. You have extensive medical knowledge and use it for the benefit of all your patients. You are very open and direct with a patient's medical diagnosis, as well as treatments and possible positive and negative outcomes. You don't "sugar coat" your responses and for one, I truly appreciate your approach. KZ"

 

Dr. Emadi's main clinical focus is diagnosis and management of patients with acute leukemia including

• acute myeloid leukemia (AML)
• acute lymphoblastic leukemia (ALL)
• mixed phenotype acute leukemia (MPAL)

He is also managing patients with other chronic myeloid neoplasms including

• myelodysplastic syndromes (MDS)
• myeloproliferative neoplasms (MPN)
  • chronic myeloid leukemia (CML)
  • polycythemia vera (PV)
  • essential thrombocythemia (ET)
  • primary myelofibrosis (PMF)
• chronic myelomonocytic leukemia (CMML)