Ralph DeBerardinis, M.D., Ph.D.

Director, Genetic and Metabolic Disease Program (CRI)

Harold C. Simmons Comprehensive Cancer Center

Sowell Family Scholar in Medical Research
Eugene McDermott Distinguished Chair for the Study of Human Growth and Development
Philip O'Bryan Montgomery Jr., M.D., Distinguished Chair in Developmental Biology

Pediatrics - Genetics and Metabolism

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Biography

Ralph DeBerardinis earned a B.S. in biology from St. Joseph's University and M.D. and Ph.D. degrees from the University of Pennsylvania. He performed his Ph.D. research on mammalian retrotransposons with Haig H. Kazazian Jr. Dr. DeBerardinis was the first trainee in the combined residency program in pediatrics and medical genetics at The Children's Hospital of Philadelphia (CHOP) and received several awards for teaching and clinical care. He ultimately achieved board certification in pediatrics, medical genetics, and clinical biochemical genetics.

Dr. DeBerardinis performed postdoctoral research in Craig Thompson's laboratory at the Penn Cancer Center from 2004 to 2007. He joined the faculty of UT Southwestern Medical Center in 2008 and joined Children’s Medical Center Research Institute at UT Southwestern (CRI) in 2011. Dr. DeBerardinis serves as Chief of Pediatric Genetics and Metabolism at UT Southwestern and Director of CRI's Genetic and Metabolic Disease Program.

Dr. DeBerardinis received Outstanding Investigator Awards from the National Cancer Institute in 2017 and 2023, and he was named an Investigator of the Howard Hughes Medical Institute in 2018. He received the Edith and Peter O'Donnell Award in Medicine from The Academy of Medicine, Engineering and Science of Texas in 2019 and the Paul Marks Prize for Cancer Research in 2021. Dr. DeBerardinis holds the Joel B. Steinberg, M.D. Distinguished Chair in Pediatrics, and he is a Sowell Family Scholar in Medical Research and a Robert L. Moody Faculty Scholar. In 2020, he was elected to the National Academy of Medicine.

He has been included in D Magazine's Best Doctors list nearly every year since 2016.

About His Laboratory

The DeBerardinis laboratory is interested in the role of altered metabolic states in human diseases, particularly pediatric inborn errors of metabolism and cancer. This research is tightly integrated with clinical activities in medical genetics, oncology, and radiology, providing seamless opportunities to examine the relevance of findings in patients.

DeBerardinis Laboratory

Education & Training

Residency - Children's Hospital of Philadelphia (2000-2005), Pediatrics & Medical Genetics
Medical School - University of Pennsylvania School of Medicine (1992-2000)

Professional Associations & Affiliations

Investigator, Howard Hughes Medical Institute (2018)
Society for Pediatrics Research
Society for Inherited Metabolic Disorders
American Society of Human Genetics
American Association for Cancer Research
American Academy of Pediatrics
American Society for Clinical Investigation
National Academy of Medicine
Association of American Physicians
Texas Academy of Medicine, Engineering, Science & Technology

Honors & Awards

National Academy of Medicine 2020
Paul Marks Prize for Cancer Research 2021
D Magazine Best Doctor, 2016, 2018-2022
D Magazine Best Pediatric Specialist 2020-2021
Edith and Peter O’Donnell Award in Medicine, The Academy of Medicine, Engineering, and Science of Texas 2018
Robert L. Moody Sr. Faculty Scholar 2017
Howard Hughes Medical Institute Faculty Scholar 2017
NCI Outstanding Investigator 2017
American Society for Clinical Investigation
Damon Runyon Cancer Research Foundation Clinical Investigator Award 2011
William K. Bowes, Jr. Award in Medical Genetics 2008
Sowell Family Scholar in Medical Research 2008
Soc. for Inherited Metabolic Disorders Neil Buist Award 2008
President’s Research Council Distinguished Young Researcher Award 2008
CHOP Pediatric Scholars Program & Faculty Honor Roll 2007

Books & Publications

Publications
- Mitochondrial complex I promotes kidney cancer metastasis.
  Bezwada D, Perelli L, Lesner NP, Cai L, Brooks B, Wu Z, Vu HS, Sondhi V, Cassidy DL, Kasitinon S, Kelekar S, Cai F, Aurora AB, Patrick M, Leach A, Ghandour R, Zhang Y, Do D, McDaniel P, Sudderth J, Dumesnil D, House S, Rosales T, Poole AM, Lotan Y, Woldu S, Bagrodia A, Meng X, Cadeddu JA, Mishra P, Garcia-Bermudez J, Pedrosa I, Kapur P, Courtney KD, Malloy CR, Genovese G, Margulis V, DeBerardinis RJ, Nature 2024 Aug
- Electron transport chain inhibition increases cellular dependence on purine transport and salvage.
  Wu Z, Bezwada D, Cai F, Harris RC, Ko B, Sondhi V, Pan C, Vu HS, Nguyen PT, Faubert B, Cai L, Chen H, Martin-Sandoval M, Do D, Gu W, Zhang Y, Zhang Y, Brooks B, Kelekar S, Zacharias LG, Oaxaca KC, Patricio JS, Mathews TP, Garcia-Bermudez J, Ni M, DeBerardinis RJ, Cell metabolism 2024 Jun
- Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples.
  Cai F, Bezwada D, Cai L, Mahar R, Wu Z, Chang MC, Pachnis P, Yang C, Kelekar S, Gu W, Brooks B, Ko B, Vu HS, Mathews TP, Zacharias LG, Martin-Sandoval M, Do D, Oaxaca KC, Jin ES, Margulis V, Malloy CR, Merritt ME, DeBerardinis RJ, Cell metabolism 2023 Aug
- In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma.
  Kaushik AK, Tarangelo A, Boroughs LK, Ragavan M, Zhang Y, Wu CY, Li X, Ahumada K, Chiang JC, Tcheuyap VT, Saatchi F, Do QN, Yong C, Rosales T, Stevens C, Rao AD, Faubert B, Pachnis P, Zacharias LG, Vu H, Cai F, Mathews TP, Genovese G, Slusher BS, Kapur P, Sun X, Merritt M, Brugarolas J, DeBerardinis RJ, Science advances 2022 Dec 8 50 eabp8293
- In vivo isotope tracing reveals a requirement for the electron transport chain in glucose and glutamine metabolism by tumors.
  Pachnis P, Wu Z, Faubert B, Tasdogan A, Gu W, Shelton S, Solmonson A, Rao AD, Kaushik AK, Rogers TJ, Ubellacker JM, LaVigne CA, Yang C, Ko B, Ramesh V, Sudderth J, Zacharias LG, Martin-Sandoval MS, Do D, Mathews TP, Zhao Z, Mishra P, Morrison SJ, DeBerardinis RJ, Science advances 2022 Sep 8 35 eabn9550
- Compartmentalized metabolism supports midgestation mammalian development.
  Solmonson A, Faubert B, Gu W, Rao A, Cowdin MA, Menendez-Montes I, Kelekar S, Rogers TJ, Pan C, Guevara G, Tarangelo A, Zacharias LG, Martin-Sandoval MS, Do D, Pachnis P, Dumesnil D, Mathews TP, Tasdogan A, Pham A, Cai L, Zhao Z, Ni M, Cleaver O, Sadek HA, Morrison SJ, DeBerardinis RJ, Nature 2022 04 604 7905 349-353
- Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer.
  Huang F, Huffman KE, Wang Z, Wang X, Li K, Cai F, Yang C, Cai L, Shih TS, Zacharias LG, Chung A, Yang Q, Chalishazar MD, Ireland AS, Stewart CA, Cargill K, Girard L, Liu Y, Ni M, Xu J, Wu X, Zhu H, Drapkin B, Byers LA, Oliver TG, Gazdar AF, Minna JD, DeBerardinis RJ, The Journal of clinical investigation 2021 Jan 131 1
- Tumor Microenvironment, Metabolism, and Immunotherapy.
  DeBerardinis RJ, The New England journal of medicine 2020 02 382 9 869-871
- Metabolic heterogeneity confers differences in melanoma metastatic potential.
  Tasdogan A, Faubert B, Ramesh V, Ubellacker JM, Shen B, Solmonson A, Murphy MM, Gu Z, Gu W, Martin M, Kasitinon SY, Vandergriff T, Mathews TP, Zhao Z, Schadendorf D, DeBerardinis RJ, Morrison SJ, Nature 2020 01 577 7788 115-120
- Mechanisms and Implications of Metabolic Heterogeneity in Cancer.
  Kim J, DeBerardinis RJ, Cell metabolism 2019 Sep 30 3 434-446
- Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells.
  Chen PH, Cai L, Huffman K, Yang C, Kim J, Faubert B, Boroughs L, Ko B, Sudderth J, McMillan EA, Girard L, Chen D, Peyton M, Shields MD, Yao B, Shames DS, Kim HS, Timmons B, Sekine I, Britt R, Weber S, Byers LA, Heymach JV, Chen J, White MA, Minna JD, Xiao G, DeBerardinis RJ, Molecular cell 2019 Sep
- Functional Assessment of Lipoyltransferase-1 Deficiency in Cells, Mice, and Humans.
  Ni M, Solmonson A, Pan C, Yang C, Li D, Notzon A, Cai L, Guevara G, Zacharias LG, Faubert B, Vu HS, Jiang L, Ko B, Morales NM, Pei J, Vale G, Rakheja D, Grishin NV, McDonald JG, Gotway GK, McNutt MC, Pascual JM, DeBerardinis RJ, Cell reports 2019 Apr 27 5 1376-1386.e6
- Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo.
  Courtney KD, Bezwada D, Mashimo T, Pichumani K, Vemireddy V, Funk AM, Wimberly J, McNeil SS, Kapur P, Lotan Y, Margulis V, Cadeddu JA, Pedrosa I, DeBerardinis RJ, Malloy CR, Bachoo RM, Maher EA Cell metabolism 2018 Aug
- Inosine Monophosphate Dehydrogenase Dependence in a Subset of Small Cell Lung Cancers.
  Huang F, Ni M, Chalishazar MD, Huffman KE, Kim J, Cai L, Shi X, Cai F, Zacharias LG, Ireland AS, Li K, Gu W, Kaushik AK, Liu X, Gazdar AF, Oliver TG, Minna JD, Hu Z, DeBerardinis RJ Cell metabolism 2018 Jun
- Genomic regression analysis of coordinated expression.
  Cai L, Li Q, Du Y, Yun J, Xie Y, DeBerardinis RJ, Xiao G Nature communications 2017 Dec 8 1 2187
- The abundance of metabolites related to protein methylation correlates with the metastatic capacity of human melanoma xenografts.
  Shi X, Tasdogan A, Huang F, Hu Z, Morrison SJ, DeBerardinis RJ Science advances 2017 Nov 3 11 eaao5268
- Lactate Metabolism in Human Lung Tumors.
  Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, Li H, Huet G, Yuan Q, Wigal T, Butt Y, Ni M, Torrealba J, Oliver D, Lenkinski RE, Malloy CR, Wachsmann JW, Young JD, Kernstine K, DeBerardinis RJ Cell 2017 Oct 171 2 358-371.e9
- CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells.
  Kim J, Hu Z, Cai L, Li K, Choi E, Faubert B, Bezwada D, Rodriguez-Canales J, Villalobos P, Lin YF, Ni M, Huffman KE, Girard L, Byers LA, Unsal-Kacmaz K, Peña CG, Heymach JV, Wauters E, Vansteenkiste J, Castrillon DH, Chen BPC, Wistuba I, Lambrechts D, Xu J, Minna JD, DeBerardinis RJ Nature 2017 Jun 546 7656 168-172
- Understanding the Intersections between Metabolism and Cancer Biology.
  Vander Heiden MG, DeBerardinis RJ Cell 2017 Feb 168 4 657-669
- Quantitative metabolic flux analysis reveals an unconventional pathway of fatty acid synthesis in cancer cells deficient for the mitochondrial citrate transport protein.
  Jiang L, Boufersaoui A, Yang C, Ko B, Rakheja D, Guevara G, Hu Z, DeBerardinis RJ Metabolic engineering 2016 Nov
- Fundamentals of cancer metabolism.
  DeBerardinis RJ, Chandel NS Science advances 2016 May 2 5 e1600200
- Reductive carboxylation supports redox homeostasis during anchorage-independent growth.
  Jiang L, Shestov AA, Swain P, Yang C, Parker SJ, Wang QA, Terada LS, Adams ND, McCabe MT, Pietrak B, Schmidt S, Metallo CM, Dranka BP, Schwartz B, DeBerardinis RJ Nature 2016 Apr 532 7598 255-8
- Metabolic Heterogeneity in Human Lung Tumors.
  Hensley CT, Faubert B, Yuan Q, Lev-Cohain N, Jin E, Kim J, Jiang L, Ko B, Skelton R, Loudat L, Wodzak M, Klimko C, McMillan E, Butt Y, Ni M, Oliver D, Torrealba J, Malloy CR, Kernstine K, Lenkinski RE, DeBerardinis RJ Cell 2016 Feb 164 4 681-94
- Metabolic pathways promoting cancer cell survival and growth.
  Boroughs LK, DeBerardinis RJ Nature cell biology 2015 Apr 17 4 351-359
- Metabolic plasticity maintains proliferation in pyruvate dehydrogenase deficient cells.
  Rajagopalan KN, Egnatchik RA, Calvaruso MA, Wasti AT, Padanad MS, Boroughs LK, Ko B, Hensley CT, Acar M, Hu Z, Jiang L, Pascual JM, Scaglioni PP, DeBerardinis RJ Cancer & metabolism 2015 3 7
- Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport.
  Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, Sudderth J, Calvaruso MA, Lumata L, Mitsche M, Rutter J, Merritt ME, DeBerardinis RJ Molecular cell 2014 Nov 56 3 414-24
- Oxidation of Alpha-Ketoglutarate Is Required for Reductive Carboxylation in Cancer Cells with Mitochondrial Defects.
  Mullen AR, Hu Z, Shi X, Jiang L, Boroughs LK, Kovacs Z, Boriack R, Rakheja D, Sullivan LB, Linehan WM, Chandel NS, DeBerardinis RJ Cell reports 2014 May
- Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer.
  Kim HS, Mendiratta S, Kim J, Pecot CV, Larsen JE, Zubovych I, Seo BY, Kim J, Eskiocak B, Chung H, McMillan E, Wu S, De Brabander J, Komurov K, Toombs JE, Wei S, Peyton M, Williams N, Gazdar AF, Posner BA, Brekken RA, Sood AK, Deberardinis RJ, Roth MG, Minna JD, White MA Cell 2013 Oct 155 3 552-66
- Mitochondrial reactive oxygen species promote epidermal differentiation and hair follicle development.
  Hamanaka RB, Glasauer A, Hoover P, Yang S, Blatt H, Mullen AR, Getsios S, Gottardi CJ, Deberardinis RJ, Lavker RM, Chandel NS Science signaling 2013 6 261 ra8
- Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo.
  Marin-Valencia I, Yang C, Mashimo T, Cho S, Baek H, Yang XL, Rajagopalan KN, Maddie M, Vemireddy V, Zhao Z, Cai L, Good L, Tu BP, Hatanpaa KJ, Mickey BE, Matés JM, Pascual JM, Maher EA, Malloy CR, Deberardinis RJ, Bachoo RM Cell metabolism 2012 Jun 15 6 827-37
- 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas.
  Choi C, Ganji SK, DeBerardinis RJ, Hatanpaa KJ, Rakheja D, Kovacs Z, Yang XL, Mashimo T, Raisanen JM, Marin-Valencia I, Pascual JM, Madden CJ, Mickey BE, Malloy CR, Bachoo RM, Maher EA Nature medicine 2012 Apr 18 4 624-9
- Cellular metabolism and disease: what do metabolic outliers teach us?
  DeBerardinis RJ, Thompson CB Cell 2012 Mar 148 6 1132-44
- Reductive carboxylation supports growth in tumour cells with defective mitochondria.
  Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, Deberardinis RJ Nature 2011 Nov
- Pyruvate carboxylase is required for glutamine-independent growth of tumor cells.
  Cheng T, Sudderth J, Yang C, Mullen AR, Jin ES, Matés JM, DeBerardinis RJ Proceedings of the National Academy of Sciences of the United States of America 2011 May 108 21 8674-9
- The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
  DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB Cell metabolism 2008 Jan 7 1 11-20
- Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis.
  DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB Proceedings of the National Academy of Sciences of the United States of America 2007 Dec 104 49 19345-50

Research

Metabolism
Inborn errors of metabolism
Genetic disorders in children
Cancer