The Laboratory of Uma Sachdeva, MD, PhD
Simches Research Center
185 Cambridge Street, 4th floor
Boston, MA 02114
Uma Sachdeva, MD, PhD
Surgeon, Division of Thoracic Surgery, Massachusetts General Hospital
Assistant Professor, Harvard Medical School
Explore This Lab
About the Lab
The Laboratory of Uma Sachdeva, MD, PhD, in the Division of Thoracic Surgery at Massachusetts General Hospital uses 3D culture models of human and mouse-derived cells to study the pathogenesis of esophageal cancer, with a focus on the role of the esophageal microenvironment in early-stage disease. We are a dynamic group of scientists and scientists-in-training from diverse backgrounds, with projects encompassing the fields of cancer cell biology, 3D epithelial organoid biology, cell metabolism and tumor-stromal interactions. Our goal is to gain better understanding of the molecular changes that accompany the development and progression of esophageal cancer, the eighth most common cancer worldwide and sixth most common cause of cancer deaths.
We welcome highly motivated trainees of all levels, including postdoctoral fellows, medical or surgical residents, and students, to contact us if interested in joining our growing team.
There are two main types of esophageal cancer:
- Squamous cell cancer (ESCC) is the more common histology in Asia and Africa, with known risk factors including several forms of toxin exposure, such as alcohol, tobacco, nitrosamines and lye
- Adenocarcinoma (EAC) is the predominant histology in Western countries, with risk factors including obesity, gastroesophageal reflux disease and Barrett’s metaplasia. While EAC shares genetic similarity with the subtype of gastric cancer characterized by chromosomal instability, the molecular mechanisms by which Barrett’s esophagus develops into dysplasia or cancer remain unknown
Using 3D organoids derived from patient samples (PDOs) or esophageal cancer cell lines, the Sachdeva Lab is studying the responses of esophageal epithelial and stromal cells to metabolic stress, and the way in which these stress response pathways contribute to malignant transformation.
Basic and translational projects in the lab focus on the following key areas:
- Investigating metabolic shifts in esophageal non-transformed epithelial and cancer cells in response to acid- and bile-induced stresses
- Determining the role of stromal-derived cytokines in promoting early esophageal cancer development
- Developing PDO libraries from normal esophageal epithelium, Barrett’s esophagus and esophageal adenocarcinoma and squamous cell carcinoma from primary patient biopsy samples
- Karakasheva TA, Gabre JT, Sachdeva UM, Cruz-Acuña R, Lin EW, DeMarshall M, Falk GW, Ginsberg GG, Yang Z, Kim MM, Diffenderfer ES, Pitarresi JR, Li J, Muir AB, Hamilton KE, Nakagawa H, Bass AJ, Rustgi AK. Patient-derived Organoids as a Platform for Modeling a Patient's Response to Chemoradiotherapy in Esophageal Cancer. Sci Rep. 2021 Oct 29;11(1):21304. doi: 10.1038/s41598-021-00706-8. PMID: 34716381; PMCID: PMC8556341
- Shimonosono M, Tanaka K, Flashner S, Takada S, Matsuura N, Tomita Y, Sachdeva UM, Noguchi E, Sangwan V, Ferri L, Momen-Heravi F, Yoon AJ, Klein-Szanto AJ, Diehl JA, Nakagawa H. Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy. Biomolecules. 2021 Oct 7;11(10):1479. doi: 10.3390/biom11101479. PMID: 34680112; PMCID: PMC8533166
- Sachdeva UM, Shimonosono M, Flashner S, Cruz-Acuña R, Gabre JT, Nakagawa H. Understanding the Cellular Origin and Progression of Esophageal Cancer Using Esophageal Organoids. Cancer Lett. 2021 Jul 1;509:39-52. doi: 10.1016/j.canlet.2021.03.031. Epub 2021 Apr 7. PMID: 33838281; PMCID: PMC8493518
- Suzuki K, Masuike Y, Mizuno R, Sachdeva UM, Chatterji P, Andres SF, Sun W, Klein-Szanto AJ, Besharati S, Remotti HE, Verzi MP, Rustgi AK. LIN28B Induces a Differentiation Program Through CDX2 in Colon Cancer. JCI Insight. 2021 May 10;6(9):e140382. doi: 10.1172/jci.insight.140382. PMID: 33755595; PMCID: PMC8262288
- Sachdeva UM, Axtell AL, Kroese TE, Chang DC, Morse CR. Impact of Obesity on Treatment Approach for Resectable Esophageal Cancer. Ann Thorac Surg. 2021 Oct;112(4):1059-1066. doi: 10.1016/j.athoracsur.2020.12.002. Epub 2020 Dec 17. PMID: 33345782
- Chandramouleeswaran PM, Guha M, Shimonosono M, Whelan KA, Maekawa H, Sachdeva UM, Ruthel G, Mukherjee S, Engel N, Gonzalez MV, Garifallou J, Ohashi S, Klein-Szanto AJ, Mesaros CA, Blair IA, Pellegrino da Silva R, Hakonarson H, Noguchi E, Baur JA, Nakagawa H. Autophagy Mitigates Ethanol-induced Mitochondrial Dysfunction and Oxidative Stress in Esophageal Keratinocytes. PLoS One. 2020 Sep 23;15(9):e0239625. doi: 10.1371/journal.pone.0239625. PMID: 32966340; PMCID: PMC7510980
- Wise DR, Ward PS, Shay JE, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB. Hypoxia Promotes Isocitrate Dehydrogenase-dependent Carboxylation of α-ketoglutarate to Citrate to Support Cell Growth and Viability. Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19611-6. doi: 10.1073/pnas.1117773108. Epub 2011 Nov 21. PMID: 22106302; PMCID: PMC3241793
- Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ, Thompson CB, Evans RM. AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation. Science. 2009 Oct 16;326(5951):437-40. doi: 10.1126/science.1172156. PMID: 19833968; PMCID: PMC2819106
- Sachdeva UM, Thompson CB. Diurnal Rhythms of Autophagy: Implications for Cell Biology and Human Disease. Autophagy. 2008 Jul;4(5):581-9. doi: 10.4161/auto.6141. Epub 2008 Apr 17. PMID: 18437053
- Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate Lyase Links Cellular Metabolism to Histone Acetylation. Science. 2009 May 22;324(5930):1076-80. doi: 10.1126/science.1164097. PMID: 19461003; PMCID: PMC2746744
Meet the Team
Uma Sachdeva, MD, PhD
Uma Sachdeva, MD, PhD, is a thoracic surgeon at Massachusetts General Hospital and Assistant Professor at Harvard Medical School. She received her MD and PhD in cell and molecular biology through the Medical Scientist Training Program at the University of Pennsylvania, after completing an undergraduate degree in biochemistry from Harvard College. She is a graduate of the MGH General Surgery and Cardiothoracic Surgery training programs. She practices all aspects of thoracic surgery, with a specific interest in thoracic oncology, including esophageal and lung cancers. She also leads a lab-based research effort studying the molecular pathways that underlie development of esophageal cancer and its precursor lesions, including Barrett’s esophagus. She is the recipient of the 2nd David C. Sabiston Research Scholarship from the American Association for Thoracic Surgery and the 2021 Research Scholarship from the Thoracic Surgery Foundation.
Pavithra Rajagopalan, PhD
Aya Tal-mason, BA
BA/MD Student, Boston University
Niamh McNamee, PhD
#1 Research Hospital in America
Mass General is the #1 hospital in New England based U.S. News & World Report Best Hospitals for 2022-2023.
Numerous Milestones in Thoracic Surgery
For more than 70 years, patients from around the world have come to the Mass General Division of Thoracic Surgery for surgical care.