Javid J. Moslehi, M.D.

Associate Professor

javid.moslehi@vanderbilt.edu
Faculty Appointments
Associate Professor of Medicine
Education
M.D., University of Connecticut School of Medicine, Farmington, ConnecticutB.A., Johns Hopkins University, Baltimore, Maryland
Research Description
An overarching focus of the Moslehi laboratory is cardio-oncology or the intersection of cardiovascular disease and cancer. General areas of interest in the laboratory include cardiovascular toxicities that occur as a result of targeted cancer therapies, adverse effects of tumors on the cardiovascular and metabolic systems, cancers that arise from the heart, and the growing appreciation that common risk factors (including genetic mutations) predispose to both cancer and cardiovascular disease. The Moslehi laboratory uses an integrated approach from molecules, cell-based and animal models, and systems biology towards these goals. As well, the laboratory is well integrated to the Vanderbilt cardio-oncology clinical program, with the hope that discoveries in the laboratory will translate into clinical practice.

Cardiovascular Toxicities of Targeted Cancer Therapies-
A major focus of the laboratory is more mechanistic understanding of cardiovascular toxicities that result from novel “targeted” cancer therapies. In this manner, the lab tests the hypothesis that the cardiovascular sequalae of novel “targeted” cancer therapies can provide fundamental insights into human cardiovascular biology (and can potentially inform cardiac drug discovery). Our program brings together basic scientists, translational biologist and clinicians and collaborates closely with oncologists and regulatory agencies nationally and internationally in this effort.

Specific areas of Interest -
1. Kinase Inhibitor-associated cardiovascular toxicity (such as nilotinib or ponatinib) – hypertension, vascular disease
2. Angiogenesis-inhibitors (specifically Vascular Endothelial Growth Factor – VEGF – signaling pathway inhibitors, such as bevacizumab or pazopanib) – hypertension, thrombosis, cardiomyopathy
3. Drugs that target protein degradation – Immunomodulators (such as lenalidomide) and proteasome inhibitors (such as carfilzomib) – hypertension, thrombosis
4. Cancer immunotherapies – myocarditis, vascular toxicity

Myotoxicity associated with immune checkpoint inhibitors-
The Moslehi laboratory has defined a new clinical syndrome of myotoxicity associated with cancer immune checkpoint inhibitors. This syndrome can present with development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and fulminant myocarditis with a robust presence of T-cell and macrophage infiltrates. We have started studies exploring the mechanisms of this new clinical syndrome, why certain cancer patients are especially at risk and the implications of this syndrome for other cardiac diseases, including other types of myocarditis and cardiac transplant rejection. Additionally, preliminary data suggest that the targets of immune checkpoint inhibitors, PD-1/PD-L1 may play a critical role in the cross talk between the cardiovascular and immune systems.

Cancer Affecting or Arising from the Cardiovascular System-
Certain cancers can have adverse effects on the cardiovascular system or may arise from cardiac tissue. For example, carcinoid tumors can affect the heart, resulting in valvular heart disease and heart failure. Other tumors can cause myocyte (both skeletal muscle and cardiac) atrophy resulting in cachexia. In other cases, cardiac tumors can arise from the heart itself. Using clinical samples collected both at Vanderbilt and in collaboration with other centers, we are dissecting the mechanisms by which cancers can interact with the cardiovascular systems in these ways.

Vanderbilt Cardio-Oncology Program-
A unique aspect of the laboratory environment is the close interaction of the laboratory with the Vanderbilt cardio-oncology program. The program now includes a clinical fellowship as well as a multidisciplinary approach to patient care with a close working relationship between cardiologists and oncologists.
Research Keywords
Cardio-Oncology, Kinase biology, Immunotherapy, Myocarditis, Induced pluripotent stem cells (iPSC), Cardiomyopathy
Publications
Moslehi J, Amgalan D, Kitsis RN. Grounding Cardio-Oncology in Basic and Clinical Science. Circulation. 2017 Jul 7/4/2017; 136(1): 3-5. PMID: 28674089, PII: CIRCULATIONAHA.117.025393, DOI: 10.1161/CIRCULATIONAHA.117.025393, ISSN: 1524-4539.

Li W, Garcia D, Cornell RF, Gailani D, Laubach J, Maglio ME, Richardson PG, Moslehi J. Cardiovascular and Thrombotic Complications of Novel Multiple Myeloma Therapies: A Review. JAMA Oncol. 2017 Jul 7/1/2017; 3(7): 980-8. PMID: 27632640, PII: 2552679, DOI: 10.1001/jamaoncol.2016.3350, ISSN: 2374-2445.

Lampson BL, Yu L, Glynn RJ, Barrientos JC, Jacobsen ED, Banerji V, Jones JA, Walewska R, Savage KJ, Michaud GF, Moslehi JJ, Brown JR. Ventricular arrhythmias and sudden death in patients taking ibrutinib [letter]. Blood [print-electronic]. 2017 May 5/4/2017; 129(18): 2581-4. PMID: 28223277, PII: blood-2016-10-742437, DOI: 10.1182/blood-2016-10-742437, ISSN: 1528-0020.

Laubach JP, Moslehi JJ, Francis SA, San Miguel JF, Sonneveld P, Orlowski RZ, Moreau P, Rosiñol L, Faber EA, Voorhees P, Mateos MV, Marquez L, Feng H, Desai A, van de Velde H, Elliott J, Shi H, Dow E, Jobanputra N, Esseltine DL, Niculescu L, Anderson KC, Lonial S, Richardson PG. A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma. Br. J. Haematol [print-electronic]. 2017 May 5/3/2017; PMID: 28466536, DOI: 10.1111/bjh.14708, ISSN: 1365-2141.

Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, Ruddy K, Lenihan D. Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J. Clin. Oncol [print-electronic]. 2017 Mar 3/10/2017; 35(8): 893-911. PMID: 27918725, PII: 10.1200/JCO.2016.70.5400, DOI: 10.1200/JCO.2016.70.5400, ISSN: 1527-7755.

Wang DY, Okoye GD, Neilan TG, Johnson DB, Moslehi JJ. Cardiovascular Toxicities Associated with Cancer Immunotherapies. Curr Cardiol Rep. 2017 Mar; 19(3): 21. PMID: 28220466, PII: 10.1007/s11886-017-0835-0, DOI: 10.1007/s11886-017-0835-0, ISSN: 1534-3170.

Sharma A, Burridge PW, McKeithan WL, Serrano R, Shukla P, Sayed N, Churko JM, Kitani T, Wu H, Holmström A, Matsa E, Zhang Y, Kumar A, Fan AC, Del Álamo JC, Wu SM, Moslehi JJ, Mercola M, Wu JC. High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Sci Transl Med. 2017 Feb 2/15/2017; 9(377): PMID: 28202772, PMCID: PMC5409837, PII: 9/377/eaaf2584, DOI: 10.1126/scitranslmed.aaf2584, ISSN: 1946-6242.

Moslehi JJ, Johnson DB, Sosman JA. Myocarditis with Immune Checkpoint Blockade [letter]. N. Engl. J. Med. 2017 Jan 1/19/2017; 376(3): 292. PMID: 28099832, DOI: 10.1056/NEJMc1615251, ISSN: 1533-4406.

Sarosiek KA, Fraser C, Muthalagu N, Bhola PD, Chang W, McBrayer SK, Cantlon A, Fisch S, Golomb-Mello G, Ryan JA, Deng J, Jian B, Corbett C, Goldenberg M, Madsen JR, Liao R, Walsh D, Sedivy J, Murphy DJ, Carrasco DR, Robinson S, Moslehi J, Letai A. Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics. Cancer Cell [print-electronic]. 2017 Jan 1/9/2017; 31(1): 142-56. PMID: 28017613, PMCID: PMC5363285, PII: S1535-6108(16)30554-2, DOI: 10.1016/j.ccell.2016.11.011, ISSN: 1878-3686.

Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA, Anders RA, Sosman JA, Moslehi JJ. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N. Engl. J. Med. 2016 Nov 11/3/2016; 375(18): 1749-55. PMID: 27806233, PMCID: PMC5247797, DOI: 10.1056/NEJMoa1609214, ISSN: 1533-4406.

Moslehi JJ. Cardiovascular Toxic Effects of Targeted Cancer Therapies. N. Engl. J. Med. 2016 Oct 10/13/2016; 375(15): 1457-67. PMID: 27732808, DOI: 10.1056/NEJMra1100265, ISSN: 1533-4406.

Denlinger CS, Ligibel JA, Are M, Baker KS, Broderick G, Demark-Wahnefried W, Friedman DL, Goldman M, Jones LW, King A, Ku GH, Kvale E, Langbaum TS, McCabe MS, Melisko M, Montoya JG, Mooney K, Morgan MA, Moslehi JJ, O'Connor T, Overholser L, Paskett ED, Peppercorn J, Rodriguez MA, Ruddy KJ, Sanft T, Silverman P, Smith S, Syrjala KL, Urba SG, Wakabayashi MT, Zee P, McMillian NR, Freedman-Cass DA. NCCN Guidelines Insights: Survivorship, Version 1.2016. J Natl Compr Canc Netw. 2016 Jun; 14(6): 715-24. PMID: 27283164, PII: 14/6/715.

Truong SR, Barry WT, Moslehi JJ, Baker EL, Mayer EL, Partridge AH. Evaluating the Utility of Baseline Cardiac Function Screening in Early-Stage Breast Cancer Treatment. Oncologist [print-electronic]. 2016 Jun; 21(6): 666-70. PMID: 27107002, PMCID: PMC4912366, PII: theoncologist.2015-0449, DOI: 10.1634/theoncologist.2015-0449, ISSN: 1549-490X.

Li W, Cornell RF, Lenihan D, Slosky D, Jagasia M, Piazza G, Moslehi J. Cardiovascular Complications of Novel Multiple Myeloma Treatments. Circulation. 2016 Mar 3/1/2016; 133(9): 908-12. PMID: 26927008, PII: CIRCULATIONAHA.115.018351, DOI: 10.1161/CIRCULATIONAHA.115.018351, ISSN: 1524-4539.

Olenchock BA, Moslehi J, Baik AH, Davidson SM, Williams J, Gibson WJ, Pierce KA, Miller CM, Hanse EA, Kelekar A, Sullivan LB, Wagers AJ, Clish CB, Vander Heiden MG, Kaelin WG. EGLN1 Inhibition and Rerouting of a-Ketoglutarate Suffice for Remote Ischemic Protection. Cell. 2016 Feb 2/25/2016; 164(5): 884-95. PMID: 26919427, PII: S0092-8674(16)30072-1, DOI: 10.1016/j.cell.2016.02.006, ISSN: 1097-4172.

Olenchock BA, Moslehi J, Baik AH, Davidson SM, Williams J, Gibson WJ, Pierce KA, Miller CM, Hanse EA, Kelekar A, Sullivan LB, Wagers AJ, Clish CB, Vander Heiden MG, Kaelin WG. EGLN1 Inhibition and Rerouting of a-Ketoglutarate Suffice for Remote Ischemic Protection. Cell. 2016 Feb 2/25/2016; 164(5): 884-95. PMID: 26919427, PII: S0092-8674(16)30072-1, DOI: 10.1016/j.cell.2016.02.006, ISSN: 1097-4172.

Bhatia N, Santos M, Jones LW, Beckman JA, Penson DF, Morgans AK, Moslehi J. Cardiovascular Effects of Androgen Deprivation Therapy for the Treatment of Prostate Cancer: ABCDE Steps to Reduce Cardiovascular Disease in Patients With Prostate Cancer. Circulation. 2016 Feb 2/2/2016; 133(5): 537-41. PMID: 26831435, PII: CIRCULATIONAHA.115.012519, DOI: 10.1161/CIRCULATIONAHA.115.012519, ISSN: 1524-4539.

Bhatia N, Santos M, Jones LW, Beckman JA, Penson DF, Morgans AK, Moslehi J. Cardiovascular Effects of Androgen Deprivation Therapy for the Treatment of Prostate Cancer: ABCDE Steps to Reduce Cardiovascular Disease in Patients With Prostate Cancer. Circulation. 2016 Feb 2/2/2016; 133(5): 537-41. PMID: 26831435, PII: CIRCULATIONAHA.115.012519, DOI: 10.1161/CIRCULATIONAHA.115.012519, ISSN: 1524-4539.

Scott JM, Armenian S, Giralt S, Moslehi J, Wang T, Jones LW. Cardiovascular disease following hematopoietic stem cell transplantation: Pathogenesis, detection, and the cardioprotective role of aerobic training. Crit. Rev. Oncol. Hematol [print-electronic]. 2016 Feb; 98: 222-34. PMID: 26643524, PII: S1040-8428(15)30077-9, DOI: 10.1016/j.critrevonc.2015.11.007, ISSN: 1879-0461.

Dang C, Guo H, Najita J, Yardley D, Marcom K, Albain K, Rugo H, Miller K, Ellis M, Shapira I, Wolff AC, Carey LA, Moy B, Groarke J, Moslehi J, Krop I, Burstein HJ, Hudis C, Winer EP, Tolaney SM. Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer. JAMA Oncol. 2016 Jan 1/1/2016; 2(1): 29-36. PMID: 26539793, PII: 2467066, DOI: 10.1001/jamaoncol.2015.3709, ISSN: 2374-2445.

Dang C, Guo H, Najita J, Yardley D, Marcom K, Albain K, Rugo H, Miller K, Ellis M, Shapira I, Wolff AC, Carey LA, Moy B, Groarke J, Moslehi J, Krop I, Burstein HJ, Hudis C, Winer EP, Tolaney SM. Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer. JAMA Oncol. 2016 Jan 1/1/2016; 2(1): 29-36. PMID: 26539793, PII: 2467066, DOI: 10.1001/jamaoncol.2015.3709, ISSN: 2374-2445.

Moslehi JJ, Deininger M. Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia. J. Clin. Oncol [print-electronic]. 2015 Dec 12/10/2015; 33(35): 4210-8. PMID: 26371140, PMCID: PMC4658454, PII: JCO.2015.62.4718, DOI: 10.1200/JCO.2015.62.4718, ISSN: 1527-7755.

Bellinger AM, Arteaga CL, Force T, Humphreys BD, Demetri GD, Druker BJ, Moslehi JJ. Cardio-Oncology: How New Targeted Cancer Therapies and Precision Medicine Can Inform Cardiovascular Discovery. Circulation. 2015 Dec 12/8/2015; 132(23): 2248-58. PMID: 26644247, PII: CIRCULATIONAHA.115.010484, DOI: 10.1161/CIRCULATIONAHA.115.010484, ISSN: 1524-4539.

Guan J, Khambhati J, Jones LW, Morgans A, Allaf M, Penson DF, Moslehi J. Cardiology Patient Page. ABCDE Steps for Heart and Vascular Wellness Following a Prostate Cancer Diagnosis. Circulation. 2015 Nov 11/3/2015; 132(18): e218-20. PMID: 26527696, PII: CIRCULATIONAHA.115.012521, DOI: 10.1161/CIRCULATIONAHA.115.012521, ISSN: 1524-4539.

Guan J, Khambhati J, Jones LW, Morgans A, Allaf M, Penson DF, Moslehi J. Cardiology Patient Page. ABCDE Steps for Heart and Vascular Wellness Following a Prostate Cancer Diagnosis. Circulation. 2015 Nov 11/3/2015; 132(18): e218-20. PMID: 26527696, PII: CIRCULATIONAHA.115.012521, DOI: 10.1161/CIRCULATIONAHA.115.012521, ISSN: 1524-4539.

Li W, Croce K, Steensma DP, McDermott DF, Ben-Yehuda O, Moslehi J. Vascular and Metabolic Implications of Novel Targeted Cancer Therapies: Focus on Kinase Inhibitors. J. Am. Coll. Cardiol. 2015 Sep 9/8/2015; 66(10): 1160-78. PMID: 26337996, PII: S0735-1097(15)04515-5, DOI: 10.1016/j.jacc.2015.07.025, ISSN: 1558-3597.

Li W, Croce K, Steensma DP, McDermott DF, Ben-Yehuda O, Moslehi J. Vascular and Metabolic Implications of Novel Targeted Cancer Therapies: Focus on Kinase Inhibitors. J. Am. Coll. Cardiol. 2015 Sep 9/8/2015; 66(10): 1160-78. PMID: 26337996, PII: S0735-1097(15)04515-5, DOI: 10.1016/j.jacc.2015.07.025, ISSN: 1558-3597.

Fradley MG, Moslehi J. QT Prolongation and Oncology Drug Development. Card Electrophysiol Clin [print-electronic]. 2015 Jun; 7(2): 341-55. PMID: 26002398, PII: S1877-9182(15)00042-8, DOI: 10.1016/j.ccep.2015.03.013, ISSN: 1877-9190.

Groarke JD, Tanguturi VK, Hainer J, Klein J, Moslehi JJ, Ng A, Forman DE, Di Carli MF, Nohria A. Abnormal exercise response in long-term survivors of hodgkin lymphoma treated with thoracic irradiation: evidence of cardiac autonomic dysfunction and impact on outcomes. J. Am. Coll. Cardiol. 2015 Feb 2/17/2015; 65(6): 573-83. PMID: 25677317, PII: S0735-1097(14)07283-0, DOI: 10.1016/j.jacc.2014.11.035, ISSN: 1558-3597.

Montazeri K, Unitt C, Foody JM, Harris JR, Partridge AH, Moslehi J. ABCDE steps to prevent heart disease in breast cancer survivors. Circulation. 2014 Oct 10/28/2014; 130(18): e157-9. PMID: 25462826, PII: 130/18/e157, DOI: 10.1161/CIRCULATIONAHA.114.008820, ISSN: 1524-4539.

Koelwyn GJ, Jones LW, Moslehi J. Unravelling the causes of reduced peak oxygen consumption in patients with cancer: complex, timely, and necessary [editorial]. J. Am. Coll. Cardiol. 2014 Sep 9/30/2014; 64(13): 1320-2. PMID: 25257632, PII: S0735-1097(14)05623-X, DOI: 10.1016/j.jacc.2014.07.949, ISSN: 1558-3597.

Zheng X, Zhai B, Koivunen P, Shin SJ, Lu G, Liu J, Geisen C, Chakraborty AA, Moslehi JJ, Smalley DM, Wei X, Chen X, Chen Z, Beres JM, Zhang J, Tsao JL, Brenner MC, Zhang Y, Fan C, DePinho RA, Paik J, Gygi SP, Kaelin WG, Zhang Q. Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Genes Dev. 2014 Jul 7/1/2014; 28(13): 1429-44. PMID: 24990963, PMCID: PMC4083087, PII: 28/13/1429, DOI: 10.1101/gad.242131.114, ISSN: 1549-5477.

Unitt C, Montazeri K, Tolaney S, Moslehi J. Cardiology patient page. Breast cancer chemotherapy and your heart. Circulation. 2014 Jun 6/24/2014; 129(25): e680-2. PMID: 24958758, PII: 129/25/e680, DOI: 10.1161/CIRCULATIONAHA.113.007181, ISSN: 1524-4539.

Akbay EA, Moslehi J, Christensen CL, Saha S, Tchaicha JH, Ramkissoon SH, Stewart KM, Carretero J, Kikuchi E, Zhang H, Cohoon TJ, Murray S, Liu W, Uno K, Fisch S, Jones K, Gurumurthy S, Gliser C, Choe S, Keenan M, Son J, Stanley I, Losman JA, Padera R, Bronson RT, Asara JM, Abdel-Wahab O, Amrein PC, Fathi AT, Danial NN, Kimmelman AC, Kung AL, Ligon KL, Yen KE, Kaelin WG, Bardeesy N, Wong KK. D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes Dev. 2014 Mar 3/1/2014; 28(5): 479-90. PMID: 24589777, PMCID: PMC3950345, PII: 28/5/479, DOI: 10.1101/gad.231233.113, ISSN: 1549-5477.

Francis SA, Cheng S, Arteaga CL, Moslehi J. Heart failure and breast cancer therapies: moving towards personalized risk assessment [editorial]. J Am Heart Assoc. 2014 Feb; 3(1): e000780. PMID: 24584746, PMCID: PMC3959702, PII: jah3455, DOI: 10.1161/JAHA.113.000780, ISSN: 2047-9980.

Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013 Dec 12/19/2013; 155(7): 1624-38. PMID: 24360282, PMCID: PMC4076149, PII: S0092-8674(13)01521-3, DOI: 10.1016/j.cell.2013.11.037, ISSN: 1097-4172.

Available Postdoctoral Position Details
Posted: 6/26/2015
A post-doctoral position is available in Dr. Moslehi||s laboratory to study the mechanisms of cardiotoxicity of novel targeted cancer therapies . Small laboratory animal models, biochemistry, molecular biology, and proteomics techniques are the main research approaches for these studies, complemented by human studies. The successful applicant will hold a Ph.D. and/or M.D. with 2 years of post-doctoral experience. Ability to work both independently and cooperatively within a team is essential. The successful candidate should demonstrate excellent scientific communication, presentation and writing skills, and analytical problem solving skills, as well as a strong work ethic.