Jeffrey C. Rathmell, Ph.D.

Professor

jeff.rathmell@vanderbilt.edu

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Faculty Appointments
Professor of Pathology, Microbiology and Immunology Professor of Cancer BiologyCornelius Vanderbilt Chair in Immunobiology
Education
Ph.D., Immunology, Stanford University, Stanford, CaliforniaB.S., Biology, University of Northern Iowa, Cedar Falls, Iowa
Research Description
No cell can survive or act without the appropriate nutrients and metabolic program. There has been a growing appreciation that metabolism is intimately linked to nearly all aspects of cell function and fate. The field of immunometabolism aims to understand how metabolic pathways are regulated in immune cells, how specific metabolic programs alter immune function, and how immunity in turn may influence metabolism. The Rathmell lab focuses on how metabolic pathways influence the function and fate of lymphocytes in inflammatory diseases, anti-tumor immunity, and in leukemia. Our work is highly interdisciplinary and involves the fields of immunology, cancer biology, and cell metabolism. Ultimately the goals of these projects are to exploit the specific metabolic programs of each cell type or activation state to selectively impact effector lymphocytes in inflammatory diseases and leukemic cells in cancer.
Research Keywords
Immunometabolism in inflammatory disease, cancer, and anti-tumor immunity
Publications
Andrejeva G, Rathmell JC. Similarities and Distinctions of Cancer and Immune Metabolism in Inflammation and Tumors. Cell Metab. 2017 Jul 7/5/2017; 26(1): 49-70. PMID: 28683294, PII: S1550-4131(17)30346-7, DOI: 10.1016/j.cmet.2017.06.004, ISSN: 1932-7420.

MacIver NJ, Rathmell JC. Editorial overview: Metabolism of T cells: integrating nutrients, signals, and cell fate [editorial]. Curr. Opin. Immunol [print-electronic]. 2017 Jul 7/3/2017; PMID: 28684058, PII: S0952-7915(17)30101-2, DOI: 10.1016/j.coi.2017.06.002, ISSN: 1879-0372.

Siska PJ, Beckermann KE, Mason FM, Andrejeva G, Greenplate AR, Sendor AB, Chiang YJ, Corona AL, Gemta LF, Vincent BG, Wang RC, Kim B, Hong J, Chen CL, Bullock TN, Irish JM, Rathmell WK, Rathmell JC. Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. JCI Insight [print-electronic]. 2017 Jun 6/15/2017; 2(12): PMID: 28614802, PMCID: PMC5470888, PII: 93411, DOI: 10.1172/jci.insight.93411, ISSN: 2379-3708.

Beckermann KE, Dudzinski SO, Rathmell JC. Dysfunctional T cell metabolism in the tumor microenvironment. Cytokine Growth Factor Rev [print-electronic]. 2017 Jun; 35: 7-14. PMID: 28456467, PII: S1359-6101(17)30052-7, DOI: 10.1016/j.cytogfr.2017.04.003, ISSN: 1879-0305.

Olenchock BA, Rathmell JC, Vander Heiden MG. Biochemical Underpinnings of Immune Cell Metabolic Phenotypes. Immunity. 2017 May 5/16/2017; 46(5): 703-13. PMID: 28514672, PII: S1074-7613(17)30178-4, DOI: 10.1016/j.immuni.2017.04.013, ISSN: 1097-4180.

Rhoads JP, Major AS, Rathmell JC. Fine tuning of immunometabolism for the treatment of rheumatic diseases. Nat Rev Rheumatol [print-electronic]. 2017 May; 13(5): 313-20. PMID: 28381829, PMCID: PMC5502208, PII: nrrheum.2017.54, DOI: 10.1038/nrrheum.2017.54, ISSN: 1759-4804.

Schmidt EA, Fee BE, Henry SC, Nichols AG, Shinohara ML, Rathmell JC, MacIver NJ, Coers J, Ilkayeva OR, Koves TR, Taylor GA. Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages. J. Biol. Chem [print-electronic]. 2017 Mar 3/17/2017; 292(11): 4651-62. PMID: 28154172, PMCID: PMC5377780, PII: M116.770735, DOI: 10.1074/jbc.M116.770735, ISSN: 1083-351X.

Siska PJ, Johnpulle RAN, Zhou A, Bordeaux J, Kim JY, Dabbas B, Dakappagari N, Rathmell JC, Rathmell WK, Morgans AK, Balko JM, Johnson DB. Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling. Oncoimmunology. 2017; 6(4): e1305535. PMID: 28507813, PMCID: PMC5414873, PII: 1305535, DOI: 10.1080/2162402X.2017.1305535, ISSN: 2162-4011.

Adams WC, Chen YH, Kratchmarov R, Yen B, Nish SA, Lin WW, Rothman NJ, Luchsinger LL, Klein U, Busslinger M, Rathmell JC, Snoeck HW, Reiner SL. Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal. Cell Rep. 2016 Dec 12/20/2016; 17(12): 3142-52. PMID: 28009285, PMCID: PMC5189677, PII: S2211-1247(16)31639-4, DOI: 10.1016/j.celrep.2016.11.065, ISSN: 2211-1247.

Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ, Nichols AG, Warmoes MO, de Cubas AA, MacIver NJ, Locasale JW, Turka LA, Wells AD, Rathmell JC. Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat. Immunol [print-electronic]. 2016 Dec; 17(12): 1459-66. PMID: 27695003, PII: ni.3577, DOI: 10.1038/ni.3577, ISSN: 1529-2916.

Siska PJ, Rathmell JC. Metabolic Signaling Drives IFN-¿. Cell Metab. 2016 Nov 11/8/2016; 24(5): 651-2. PMID: 27829134, PII: S1550-4131(16)30550-2, DOI: 10.1016/j.cmet.2016.10.018, ISSN: 1932-7420.

Siska PJ, Kim B, Ji X, Hoeksema MD, Massion PP, Beckermann KE, Wu J, Chi JT, Hong J, Rathmell JC. Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes. J. Immunol. Methods [print-electronic]. 2016 Nov; 438: 51-8. PMID: 27594594, PMCID: PMC5065394, PII: S0022-1759(16)30188-0, DOI: 10.1016/j.jim.2016.08.013, ISSN: 1872-7905.

Johnson MO, Siska PJ, Contreras DC, Rathmell JC. Nutrients and the microenvironment to feed a T cell army. Semin. Immunol [print-electronic]. 2016 Oct 10/3/2016; PMID: 27712958, PII: S1044-5323(16)30096-3, DOI: 10.1016/j.smim.2016.09.003, ISSN: 1096-3618.

Zeng H, Cohen S, Guy C, Shrestha S, Neale G, Brown SA, Cloer C, Kishton RJ, Gao X, Youngblood B, Do M, Li MO, Locasale JW, Rathmell JC, Chi H. MTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation. Immunity [print-electronic]. 2016 Sep 9/20/2016; 45(3): 540-54. PMID: 27637146, PMCID: PMC5050556, PII: S1074-7613(16)30341-7, DOI: 10.1016/j.immuni.2016.08.017, ISSN: 1097-4180.

Siska PJ, van der Windt GJ, Kishton RJ, Cohen S, Eisner W, MacIver NJ, Kater AP, Weinberg JB, Rathmell JC. Suppression of Glut1 and Glucose Metabolism by Decreased Akt/mTORC1 Signaling Drives T Cell Impairment in B Cell Leukemia. J. Immunol [print-electronic]. 2016 Sep 9/15/2016; 197(6): 2532-40. PMID: 27511728, PMCID: PMC5010978, PII: jimmunol.1502464, DOI: 10.4049/jimmunol.1502464, ISSN: 1550-6606.

O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol [print-electronic]. 2016 Jul 7/11/2016; PMID: 27396447, PII: nri.2016.70, DOI: 10.1038/nri.2016.70, ISSN: 1474-1741.

Kishton RJ, Barnes CE, Nichols AG, Cohen S, Gerriets VA, Siska PJ, Macintyre AN, Goraksha-Hicks P, de Cubas AA, Liu T, Warmoes MO, Abel ED, Yeoh AE, Gershon TR, Rathmell WK, Richards KL, Locasale JW, Rathmell JC. AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival. Cell Metab. 2016 Apr 4/12/2016; 23(4): 649-62. PMID: 27076078, PMCID: PMC4832577, PII: S1550-4131(16)30111-5, DOI: 10.1016/j.cmet.2016.03.008, ISSN: 1932-7420.

Hosios AM, Hecht VC, Danai LV, Johnson MO, Rathmell JC, Steinhauser ML, Manalis SR, Vander Heiden MG. Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells. Dev. Cell. 2016 Mar 3/7/2016; 36(5): 540-9. PMID: 26954548, PMCID: PMC4766004, PII: S1534-5807(16)30036-3, DOI: 10.1016/j.devcel.2016.02.012, ISSN: 1878-1551.

Johnson MO, Rathmell JC. AIF Is "Always In Fashion" for T Cells. Immunity. 2016 Jan 1/19/2016; 44(1): 11-3. PMID: 26789917, PII: S1074-7613(15)00541-5, DOI: 10.1016/j.immuni.2015.12.015, ISSN: 1097-4180.

Kang S, Keener AB, Jones SZ, Benschop RJ, Caro-Maldonado A, Rathmell JC, Clarke SH, Matsushima GK, Whitmire JK, Vilen BJ. IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF. J. Immunol [print-electronic]. 2016 Jan 1/1/2016; 196(1): 196-206. PMID: 26621863, PMCID: PMC4684997, PII: jimmunol.1402527, DOI: 10.4049/jimmunol.1402527, ISSN: 1550-6606.

Altman BJ, Hsieh AL, Sengupta A, Krishnanaiah SY, Stine ZE, Walton ZE, Gouw AM, Venkataraman A, Li B, Goraksha-Hicks P, Diskin SJ, Bellovin DI, Simon MC, Rathmell JC, Lazar MA, Maris JM, Felsher DW, Hogenesch JB, Weljie AM, Dang CV. MYC Disrupts the Circadian Clock and Metabolism in Cancer Cells. Cell Metab [print-electronic]. 2015 Dec 12/1/2015; 22(6): 1009-19. PMID: 26387865, PII: S1550-4131(15)00460-X, DOI: 10.1016/j.cmet.2015.09.003, ISSN: 1932-7420.

Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin AR, Amin A, Aquilano K, Arbiser J, Arreola A, Arzumanyan A, Ashraf SS, Azmi AS, Benencia F, Bhakta D, Bilsland A, Bishayee A, Blain SW, Block PB, Boosani CS, Carey TE, Carnero A, Carotenuto M, Casey SC, Chakrabarti M, Chaturvedi R, Chen GZ, Chen H, Chen S, Chen YC, Choi BK, Ciriolo MR, Coley HM, Collins AR, Connell M, Crawford S, Curran CS, Dabrosin C, Damia G, Dasgupta S, DeBerardinis RJ, Decker WK, Dhawan P, Diehl AM, Dong JT, Dou QP, Drew JE, Elkord E, El-Rayes B, Feitelson MA, Felsher DW, Ferguson LR, Fimognari C, Firestone GL, Frezza C, Fujii H, Fuster MM, Generali D, Georgakilas AG, Gieseler F, Gilbertson M, Green MF, Grue B, Guha G, Halicka D, Helferich WG, Heneberg P, Hentosh P, Hirschey MD, Hofseth LJ, Holcombe RF, Honoki K, Hsu HY, Huang GS, Jensen LD, Jiang WG, Jones LW, Karpowicz PA, Keith WN, Kerkar SP, Khan GN, Khatami M, Ko YH, Kucuk O, Kulathinal RJ, Kumar NB, Kwon BS, Le A, Lea MA, Lee HY, Lichtor T, Lin LT, Locasale JW, Lokeshwar BL, Longo VD, Lyssiotis CA, MacKenzie KL, Malhotra M, Marino M, Martinez-Chantar ML, Matheu A, Maxwell C, McDonnell E, Meeker AK, Mehrmohamadi M, Mehta K, Michelotti GA, Mohammad RM, Mohammed SI, Morre DJ, Muralidhar V, Muqbil I, Murphy MP, Nagaraju GP, Nahta R, Niccolai E, Nowsheen S, Panis C, Pantano F, Parslow VR, Pawelec G, Pedersen PL, Poore B, Poudyal D, Prakash S, Prince M, Raffaghello L, Rathmell JC, Rathmell WK, Ray SK, Reichrath J, Rezazadeh S, Ribatti D, Ricciardiello L, Robey RB, Rodier F, Rupasinghe HP, Russo GL, Ryan EP, Samadi AK, Sanchez-Garcia I, Sanders AJ, Santini D, Sarkar M, Sasada T, Saxena NK, Shackelford RE, Shantha Kumara HM, Sharma D, Shin DM, Sidransky D, Siegelin MD, Signori E, Singh N, Sivanand S, Sliva D, Smythe C, Spagnuolo C, Stafforini DM, Stagg J, Subbarayan PR, Sundin T, Talib WH, Thompson SK, Tran PT, Ungefroren H, Vander Heiden MG, Venkateswaran V, Vinay DS, Vlachostergios PJ, Wang Z, Wellen KE, Whelan RL, Yang ES, Yang H, Yang X, Yaswen P, Yedjou C, Yin X, Zhu J, Zollo M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin. Cancer Biol. 2015 Dec; 35 Suppl: S276-304. PMID: 26590477, PMCID: PMC4819002, PII: S1044-579X(15)00088-7, DOI: 10.1016/j.semcancer.2015.09.007, ISSN: 1096-3650.

Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui YC, Cui G, Micevic G, Perales JC, Kleinstein SH, Abel ED, Insogna KL, Feske S, Locasale JW, Bosenberg MW, Rathmell JC, Kaech SM. Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses. Cell [print-electronic]. 2015 Sep 9/10/2015; 162(6): 1217-28. PMID: 26321681, PMCID: PMC4567953, PII: S0092-8674(15)01025-9, DOI: 10.1016/j.cell.2015.08.012, ISSN: 1097-4172.

Siska PJ, Rathmell JC. PKCs Sweeten Cell Metabolism by Phosphorylation of Glut1. Mol. Cell. 2015 Jun 6/4/2015; 58(5): 711-2. PMID: 26046643, PII: S1097-2765(15)00392-5, DOI: 10.1016/j.molcel.2015.05.025, ISSN: 1097-4164.

Zhang M, Qiu Q, Li Z, Sachdeva M, Min H, Cardona DM, DeLaney TF, Han T, Ma Y, Luo L, Ilkayeva OR, Lui K, Nichols AG, Newgard CB, Kastan MB, Rathmell JC, Dewhirst MW, Kirsch DG. HIF-1 Alpha Regulates the Response of Primary Sarcomas to Radiation Therapy through a Cell Autonomous Mechanism. Radiat. Res [print-electronic]. 2015 Jun; 183(6): 594-609. PMID: 25973951, PII: 10.1667/RR14016.1, DOI: 10.1667/RR14016.1, ISSN: 1938-5404.

Siska PJ, Rathmell JC. T cell metabolic fitness in antitumor immunity. Trends Immunol [print-electronic]. 2015 Apr; 36(4): 257-64. PMID: 25773310, PMCID: PMC4393792, PII: S1471-4906(15)00038-1, DOI: 10.1016/j.it.2015.02.007, ISSN: 1471-4981.

Kishton RJ, Rathmell JC. Novel therapeutic targets of tumor metabolism. Cancer J. 2015 Mar; 21(2): 62-9. PMID: 25815845, PMCID: PMC4380246, PII: 00130404-201503000-00004, DOI: 10.1097/PPO.0000000000000099, ISSN: 1540-336X.

Kountikov EI, Poe JC, Maclver NJ, Rathmell JC, Tedder TF. A spontaneous deletion within the desmoglein 3 extracellular domain of mice results in hypomorphic protein expression, immunodeficiency, and a wasting disease phenotype. Am. J. Pathol [print-electronic]. 2015 Mar; 185(3): 617-30. PMID: 25542773, PMCID: PMC4348474, PII: S0002-9440(14)00669-5, DOI: 10.1016/j.ajpath.2014.10.025, ISSN: 1525-2191.

Huynh A, DuPage M, Priyadharshini B, Sage PT, Quiros J, Borges CM, Townamchai N, Gerriets VA, Rathmell JC, Sharpe AH, Bluestone JA, Turka LA. Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability. Nat. Immunol [print-electronic]. 2015 Feb; 16(2): 188-96. PMID: 25559257, PMCID: PMC4297515, PII: ni.3077, DOI: 10.1038/ni.3077, ISSN: 1529-2916.

Gerriets VA, Kishton RJ, Nichols AG, Macintyre AN, Inoue M, Ilkayeva O, Winter PS, Liu X, Priyadharshini B, Slawinska ME, Haeberli L, Huck C, Turka LA, Wood KC, Hale LP, Smith PA, Schneider MA, MacIver NJ, Locasale JW, Newgard CB, Shinohara ML, Rathmell JC. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J. Clin. Invest [print-electronic]. 2015 Jan; 125(1): 194-207. PMID: 25437876, PMCID: PMC4382238, PII: 76012, DOI: 10.1172/JCI76012, ISSN: 1558-8238.

Stathem M, Marimuthu S, O'Neal J, Rathmell JC, Chesney JA, Beverly LJ, Siskind LJ. Glucose availability and glycolytic metabolism dictate glycosphingolipid levels. J. Cell. Biochem. 2015 Jan; 116(1): 67-80. PMID: 25145677, PMCID: PMC4229434, DOI: 10.1002/jcb.24943, ISSN: 1097-4644.

Martz CA, Ottina KA, Singleton KR, Jasper JS, Wardell SE, Peraza-Penton A, Anderson GR, Winter PS, Wang T, Alley HM, Kwong LN, Cooper ZA, Tetzlaff M, Chen PL, Rathmell JC, Flaherty KT, Wargo JA, McDonnell DP, Sabatini DM, Wood KC. Systematic identification of signaling pathways with potential to confer anticancer drug resistance. Sci Signal. 2014 Dec 12/23/2014; 7(357): ra121. PMID: 25538079, PMCID: PMC4353587, PII: 7/357/ra121, DOI: 10.1126/scisignal.aaa1877, ISSN: 1937-9145.

Wang B, Liu TY, Lai CH, Rao YH, Choi MC, Chi JT, Dai JW, Rathmell JC, Yao TP. Glycolysis-dependent histone deacetylase 4 degradation regulates inflammatory cytokine production. Mol. Biol. Cell [print-electronic]. 2014 Nov 11/1/2014; 25(21): 3300-7. PMID: 25187650, PMCID: PMC4214777, PII: mbc.E13-12-0757, DOI: 10.1091/mbc.E13-12-0757, ISSN: 1939-4586.

Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab [print-electronic]. 2014 Jul 7/1/2014; 20(1): 61-72. PMID: 24930970, PMCID: PMC4079750, PII: S1550-4131(14)00212-5, DOI: 10.1016/j.cmet.2014.05.004, ISSN: 1932-7420.

Caro-Maldonado A, Wang R, Nichols AG, Kuraoka M, Milasta S, Sun LD, Gavin AL, Abel ED, Kelsoe G, Green DR, Rathmell JC. Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells. J. Immunol [print-electronic]. 2014 Apr 4/15/2014; 192(8): 3626-36. PMID: 24616478, PMCID: PMC3984038, PII: jimmunol.1302062, DOI: 10.4049/jimmunol.1302062, ISSN: 1550-6606.

Freemerman AJ, Johnson AR, Sacks GN, Milner JJ, Kirk EL, Troester MA, Macintyre AN, Goraksha-Hicks P, Rathmell JC, Makowski L. Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J. Biol. Chem [print-electronic]. 2014 Mar 3/14/2014; 289(11): 7884-96. PMID: 24492615, PMCID: PMC3953299, PII: M113.522037, DOI: 10.1074/jbc.M113.522037, ISSN: 1083-351X.

Liu T, Kishton RJ, Macintyre AN, Gerriets VA, Xiang H, Liu X, Abel ED, Rizzieri D, Locasale JW, Rathmell JC. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis. Cell Death Dis. 2014; 5: e1470. PMID: 25321477, PMCID: PMC4237255, PII: cddis2014431, DOI: 10.1038/cddis.2014.431, ISSN: 2041-4889.

Cao Y, Rathmell JC, Macintyre AN. Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells. PLoS ONE. 2014; 9(8): e104104. PMID: 25090630, PMCID: PMC4121309, PII: PONE-D-14-06298, DOI: 10.1371/journal.pone.0104104, ISSN: 1932-6203.

Arreola A, Cowey CL, Coloff JL, Rathmell JC, Rathmell WK. HIF1a and HIF2a exert distinct nutrient preferences in renal cells. PLoS ONE. 2014; 9(5): e98705. PMID: 24879016, PMCID: PMC4039535, PII: PONE-D-13-47383, DOI: 10.1371/journal.pone.0098705, ISSN: 1932-6203.

Saucillo DC, Gerriets VA, Sheng J, Rathmell JC, Maciver NJ. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J. Immunol [print-electronic]. 2014 Jan 1/1/2014; 192(1): 136-44. PMID: 24273001, PMCID: PMC3872216, PII: jimmunol.1301158, DOI: 10.4049/jimmunol.1301158, ISSN: 1550-6606.

Kim JS, Sklarz T, Banks LB, Gohil M, Waickman AT, Skuli N, Krock BL, Luo CT, Hu W, Pollizzi KN, Li MO, Rathmell JC, Birnbaum MJ, Powell JD, Jordan MS, Koretzky GA. Natural and inducible TH17 cells are regulated differently by Akt and mTOR pathways. Nat. Immunol [print-electronic]. 2013 Jun; 14(6): 611-8. PMID: 23644504, PMCID: PMC3711189, PII: ni.2607, DOI: 10.1038/ni.2607, ISSN: 1529-2916.

Macintyre AN, Rathmell JC. Activated lymphocytes as a metabolic model for carcinogenesis. Cancer Metab. 2013; 1(1): 5. PMID: 24280044, PMCID: PMC3834493, PII: 2049-3002-1-5, DOI: 10.1186/2049-3002-1-5, ISSN: 2049-3002.