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Ralph DeBerardinis Lab

Research Focus

Proper control of metabolism is required for essentially every biological process. Altered metabolism at the cellular level contributes to many diseases, including inborn errors of metabolism (the result of inherited genetic defects in metabolic enzymes that lead to chemical imbalances in children) and cancer. Our laboratory seeks to characterize these metabolic disorders, understand how they compromise tissue function, develop methods to monitor metabolism in vivo, and design therapies to restore normal metabolism and improve health.

In cancer, we study how oncogenic control of metabolism supports tumor initiation and progression. In inborn errors of metabolism, we use metabolomics and genomics to identify new disease genes and deepen our understanding of metabolism’s role in human health. Our research is closely integrated with clinical activities in medical genetics, oncology, and radiology, providing seamless opportunities to examine the relevance of our findings in patients.

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….
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Research Projects

Select Publications

Research Publications

Bezwada, D., Perelli, L, Lesner, N.P., Cai, L., Brooks, B., Wu, Z., Vu, H.S., Sondhi, V., Cassidy, D.L., Kasitinon, S., Kelekar, S., Cai, F., Aurora, A.B., Patrick, M., Leach, A., Ghandour, R., Zhang, Y., Do, D., McDaniel, P., Sudderth, J., Dumesnil, D., House, S., Rosales, T., Poole, A.M., Lotan, Y., Woldu, S., Bagrodia, A., Meng, X., Cadeddu, J.A., Mishra, P., Garcia-Bermudez, J., Pedrosa, I., Kapur, P., Courtney, K.D., Malloy, C.R., Genovese, G., Margulis, V. and R.J. DeBerardinis. (2024). Mitochondrial complex I promotes kidney cancer metastasis. Nature 633, 923-31. (PubMed)

Wu, Z., Bezwada, D., Cai, F., Harris, R.C., Ko, B., Sondhi, V., Pan, C., Vu, H.S., Nguyen, P.T., Faubert, B., Cai, L., Chen, H., Martin-Sandoval, M., Do, D., Gu, W., Zhang, Y., Zhang, Y., Brooks, B., Kelekar, S., Zacharias, L.G., Oaxaca, K.C., Patricio, J.S., Mathews, T.P., Garcia-Bermudez, J., Ni, M., and R.J. DeBerardinis. (2024). Electron transport chain inhibition increases cellular dependence on puring transport and salvage. Cell Metabolism 36, 1504-20. (PubMed)

Cai, F., Bezwada, D., Cai, L., Mahar, R., Wu, Z., Chang, M.C., Pachnis, P., Yang, C., Kelekar, S., Gu, W., Brooks, B., Ko, B., Vu, H.S., Mathews, T.P., Zacharias, L.G., Martin-Sandoval, M., Do, D., Oaxaca, K.C., Jin, E.S., Margulis, V., Malloy, C.R., Merritt, M.E., and R.J. DeBerardinis. (2023). Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples. Cell Metabolism 35, 1830-184. (PubMed)

Kaushik, A.K., Tarangelo, A., Boroughs, L.K., Ragavan, M., Zhang, Y., Wu, C.Y., Li, X., Ahumada, K., Chiang, J.C., Tcheuyap, V.T., Saatchi, F., Do, Q.N., Yong, C., Rosales, T., Stevens, C., Rao, A.D., Faubert, B., Pachnis, P., Zacharias, L.G., Vu, H., Cai, F., Mathews, T.P., Genovese, G., Slusher, B.S., Kapur, P., Sun, X., Merritt, M., Brugarolas, J, and R.J. DeBerardinis. (2022). In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma. Science Advances 8:eabp8293. (PubMed)

Solmonson, A., Faubert, B., Gu, W., Rao, A., Cowdin, M.A., Mendez-Monte, I., Kelekar, S., Rogers, T.J., Pan, C., Guevara, G., Tarangelo, A., Zacharias, L.G., Martin-Sandoval, M.S., Do, D., Pachnis, P., Dumesnil, D., Mathews, T., Tasdogan, A., Pham, A., Cai, L., Zhao, Z., Ni, M., Cleaver, O., Sadek, H.A., Morrison, S.J., and R.J. DeBerardinis. (2022). Compartmentalized metabolism supports midgestation mammalian development. Nature 604, 349-353. (PubMed)

Pachnis, P., Wu, Z., Faubert, B., Tasdogan, A., Gu, W., Shelton, S., Solmonson, A., Rao, A.D, Kaushik, A.K., Rogers, T.J., Ubellacker, J.M., LaVigne, C.A., Yang, C., Ko, B., Ramesh, V., Sudderth, J., Zacharias, L.G., Martin-Sandoval, M.S., Do, D., Mathews, T.P., Zhao, Z., Mishra, P., Morrison, S.J., and R.J. DeBerardinis. (2022). In vivo isotope tracing reveals a requirement for the electron transport chain in glucose and glutamine metabolism by tumors. Science Advances 8:eabn9550. (PubMed)

Huang, F., Huffman, K.E., Wang, Z., Wang, X., Cai, F., Yang, C., Cai, L., Shih, T., Zacharias, L.G., Chung, A., Yang, Q., Chalishazar, M.D., Ireland, A.S., Stewart, C.A., Cargill, K., Girard, L., Liu, Y., Ni, M., Xu, J., Wu, X., Zhu, H., Drapkin, B., Oliver, T.G., Byers, L.G., Gazdar, A.F., Minna, J.D., and R.J. DeBerardinis. (2021). Guanosine triphosphate couples oncogenic MYC’s metabolic and ribosome programs. Journal of Clinical Investigation 131:e139929. (PubMed)

Tasdogan, A., Faubert, B., Ramesh, V., Ubellacker, J.M., Shen, B., Solmonson, A., Murphy, M.M., Gu, Z., Gu, W., Martin, M., Kasitinon, S.Y., Vandergriff, T., Mathews, T.P., Zhao, Z., Schadendorf, D., DeBerardinis, R.J., and S.J. Morrison. (2020). Metabolic heterogeneity confers differences in melanoma metastatic potential. Nature 577, 115-120. (PubMed)

Chen, P.H., Cai, L., Huffman, K., Yang, C., Kim, J., Faubert, B., Boroughs, L., Ko, B., Sudderth, J., McMillan, E.A., Girard, L., Chen, D., Peyton, M., Shields, M.D., Yao, B., Shames, D.S., Kim, H.S., Timmons, B., Sekine, I., Britt, R., Weber, S., Byers, L.A., Heymach, J.V., Chen, J., White, M.A., Minna, J.D., Xiao, G., and R.J. DeBerardinis. (2019). Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells. Molecular Cell 76, 838-851. (PubMed)

Ni, M., Solmonson, A., Pan, C., Yang, C., Li, D., Notzon, A., Cai, L., Guevara, G., Zacharias, L.G., Faubert, B., Vu, H.S., Jiang, L., Ko, B., Morales, N.M., Pei, J., Vale, G., Rakheja, D., Grishin, N.V., McDonald, J.G., Gotway, G.K., McNutt, M.C., Pascual, J.M., and R.J. DeBerardinis. (2019) Functional Assessment of Lipoyltransferase- Deficiency in Cells, Mice, and Humans. Cell Reports 27, 1376-1386. (PubMed)

Huang, F., Ni, M., Chalishazar, M.D., Huffman, K.E., Kim, J., Cai, L., Shi, X., Cai, F., Zacharias, L.G., Ireland, A.S., Li, K., Gu, W., Kaushik, A.K., Liu, X., Gazdar, A.F., Oliver, T.G., Minna, J.D., Hu, Z., and R.J. DeBerardinis. (2018). Inosine Monophosphate Dehydrogenase Dependence in a Subset of Small Cell Lung Cancers. Cell Metabolism 28, 369-382. (PubMed)

Faubert, B., Li, K.Y., Cai, L., Hensley, C.T., Kim, J., Zacharias, L.G., Yang, C., Do, Q.N., Doucette, S., Burguete, D., Li, H., Huet, G., Yuan, Q., Wigal, T., Butt, Y., Ni, M., Torrealba, J., Oliver, D., Lenkinski, R.E., Malloy, C.R., Wachsmann, J.W, Young, J.D., Kernstine, K., and R.J. DeBerardinis. (2017) Lactate Metabolism in Human Lung Tumors. Cell 171, 358-371. (PubMed)

Kim, J., Hu, Z., Cai, L., Li, K., Choi, E., Faubert, B., Bezwada, D., Rodriguez-Canales, J., Villalobos, P., Lin, Y-F., Ni, M., Huffman, K.E., Girard, L., Byers, L.A., Unsal-Kacmaz, K., Peña, C.G., Heymach, J.V., Wauters, E., Vansteenkiste, J., Castrillon, D.H., Chen, B.P.C., Wistuba, I,, Lambrechts, D., Xu, J., Minna, J.D., and R.J. DeBerardinis. (2017). CPS1 maintains pyrimidine pools and DNA synthesis is KRAS/LKB1-mutant lung cancer cells. Nature 546, 168-172. (PubMed)

Hensley, C.T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., et al. (2016). Metabolic heterogeneity in human lung tumors. Cell 164, 681–694. (PubMed)

Jiang, L., Shestov, A.A., Swain, P., Yang, C., Parker, S.J., Wang, Q.A., Terada, L.S., Adams, N.D., McCabe, M.T., Pietrak, B., et al. (2016). Reductive carboxylation supports redox homeostasis during anchorage-independent growth. Nature 532, 255–258. (PubMed)

Reviews

Bartman, C.R., Faubert, B., Rabinowitz, J.D. and R.J. DeBerardinis. (2023). Metabolic pathway analysis using stable isotopes in patients with cancer. Nature Reviews Cancer 23, 863-878. (PubMed)

DeBerardinis R.J. and Keshari K.R. Metabolic analysis as a driver for discovery, diagnosis and therapy. (2022) Cell 85, 2678-2689. (PubMed)

Faubert, B., Solmonson, A., and DeBerardinis, R.J. (2020). Metabolic reprogramming and cancer progression. Science 368: eaaw5473. (Full Text)

DeBerardinis R.J. and Chandel N.S. We need to talk about the Warburg effect. (2020) Nature Metabolism 2, 127-129. (PubMed)

DeBerardinis, R.J. (2020). Tumor Microenvironment, Metabolism, and Immunotherapy. New England Journal of Medicine 382, 869-871. (PubMed)

DeBerardinis R.J. and Chandel NS. Fundamentals of cancer metabolism. (2016). Science Advances 2:e1600200. (PubMed)

 

Lab Members

Divya Bezwada, Ph.D.

Postdoctoral Fellow, Scripps Research
Ph.D. Student, Ruth L. Kirschstein NRSA Predoctoral Fellow (2016-2023)

Lindsey Boroughs, Ph.D.

Executive Medical Science Liaison, Bristol Myers Squibb
Postdoctoral Fellow (2013-2016)

Ling Cai, Ph.D., Peter O’Donnell Jr. School of Public Health

Assistant Professor, Quantitative Biomedical Research Center, UT Southwestern
Postdoctoral Fellow (2014-2016)

Mary Calvaruso, Ph.D.

Instructor, Department of Biotechnology and Biology, Biccocca University
Visiting Fellow (2013-2014)

Tzuling Cheng, Ph.D.

Associate Director, Arcus Biosciences
Postdoctoral Fellow (2009-2012)

Pei-Hsuan Chen, Ph.D.

Scientist, Vertex Pharmaceuticals
Ph.D. Student (2010-2015)

Daniel de los Santos

Emergency Medicine Residency, University of Virginia
Undergraduate Green Fellow (2014)

Robert Egnatchik, Ph.D.

Senior Research and Development Engineer, PepsiCo
Postdoctoral Fellow (2014-2016)

Brandon Faubert, Ph.D.

Assistant Professor, Department of Medicine, University of Chicago
Canadian Institutes of Health Research Fellow (2015-2021)

Rob Harris, Ph.D.

MSTP Student, UT Southwestern Medical School
M.D./Ph.D Student (2016-2021)

Lea Abou Haidar, M.D.

Pediatric Resident, UT Southwestern Medical Center
Postdoctoral Fellow (2022 – 2023)

Christopher Hensley, M.D., Ph.D.

Radiologist, Crozer Health
M.D./Ph.D. Student (2011-2015)

Zeping Hu, Ph.D.

Assistant Professor, Tsinghua University
Assistant Professor (2012-2016)

Fang Huang, M.D., Ph.D.

Associate Professor and Attending Physician in Thoracic Oncology at Huazhong University of Science and Technology
Postdoctoral Fellow (2016-2020)

Lei Jiang, Ph.D.

Assistant Professor, City of Hope
Assistant Instructor (2009-2017)

Akash Kaushik, Ph.D.

Senior Scientist, Internal Medicine Research Unit, Pfizer
Postdoctoral Fellow (2016-2022)

Sherwin Kelekar, Ph.D.

MSTP Student, UT Southwestern Medical School
M.D./Ph.D Student (2016-2022)

Jiyeon Kim, Ph.D.

Assistant Professor, University of Illinois at Chicago
Postdoctoral Fellow (2012-2018)

Sabin Kshattry, M.D., Ph.D

Resident, Yale School of Medicine
Undergraduate Green Fellow (2011)

Michael Lee, Ph.D.

MSTP Student, UT Southwestern Medical School
M.D./Ph.D. Student (2018-2024)

Andrew Mullen, Ph.D.

Director, Business Development, MEI Pharma
Ph.D. Student (2008-2013)

Hien Nguyen, Ph.D.

Senior Scientist, Moderna
Postdoctoral Fellow (2011-2012)

Min Ni, Ph.D.

Faculty, St. Jude
Associate Professor, Research (2014-2023)

Kristell Oizel, Ph.D.

Postdoctoral Fellow, Health Research Institute of the University of Nantes
Visiting Postdoctoral Fellow (2016-2017)

Panayotis Pachnis, MBBS, Ph.D.

Pediatrics Residency, UT Southwestern
Postdoctoral Fellow (2018-2021)

Pavel Pichurin, M.D., Ph.D.

Medical Geneticist, Mayo Clinic
Postdoctoral Fellow (2009-2011)

Alan Poole, M.D., Ph.D.

Assistant Professor, Pediatric Critical Care, UT Southwestern
Clinical Fellow (2016-2020)

Kartik Rajagopalan, M.D., Ph.D.

Assistant Professor, Internal Medicine, UT Southwestern Medical School
M.D./Ph.D. Student (2010-2014)

Aparna Rao, MBBS, Ph.D.

Postdoctoral Scientist and Medical Oncologist, Peter MacCallum Cancer Centre
Postdoctoral Fellow (2018-2021)

Thomas Rogers, Ph.D.

Staff Scientist, Van Andel Institute
NCI Postdoctoral Fellow (2017-2022)

Tracy Rosales, Ph.D.

Field Application Scientist, ChemoMetec
Ph.D. Student, CPRIT Predoctoral Trainee (2017-2022)

Xiaolei Shi, Ph.D.

Physician-Scientist Training Program, Internal Medicine Residency, University of Minnesota
Ph.D. Student and HHMI International Student

Ashley Solmonson, Ph.D.

Assistant Professor, Green Center for Reproductive Biology Sciences, UT Southwestern
Ruth L. Kirschstein NRSA Fellow (2016-2023)

Danny Vu, Ph.D.

Scientist, St. Jude
Senior Research Scientist (2017-2023)

Ajla Wasti, M.D.

Locum Consultant Pediatric Oncology, University College London Hospitals NHS Foundation Trust
Clinical Fellow (2012-2014)

Faith Zhang, M.D., Ph.D.

Assistant Professor, Radiation Oncology, UT Southwestern Medical Center
Clinical Fellow (2018 – 2023)

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