Silpa Gampala, PhD
Assistant Research Professor of Pediatrics
- Phone
- (317) 278-0579
- Address
-
R3 C238
PHMB
Indianapolis, IN 46202
Bio
My research focuses on identifying metabolic and redox-driven vulnerabilities in malignant peripheral nerve sheath tumors (MPNST) and pancreatic cancer, with the goal of translating these dependencies into mechanism-based therapeutic strategies. My work sits at the intersection of tumor metabolism, redox signaling, and microenvironmental adaptation, with particular emphasis on how metabolic rewiring supports tumor survival, immune evasion, and therapeutic resistance. A key area of my research has been defining the role of Ref-1/APE1 redox signaling in transcriptional and metabolic adaptation, including studies demonstrating that Ref-1 redox activity alters tumor metabolic programming and represents a targetable vulnerability in pancreatic cancer and MPNST. More recently, I have contributed to the preclinical development and validation of next-generation Ref-1 inhibitors with improved translational potential. My research program integrates patient-derived cell lines and xenograft models with metabolic flux, nutrient-stress, hypoxia, 3D co-culture, and in vivo therapeutic studies in syngeneic, PDX, and genetically engineered mouse models. Supported by competitive career development awards, my current work focuses on understanding how tumor-intrinsic metabolic rewiring intersects with the tumor microenvironment (immune and non-immune) to shape therapeutic response, with the long-term goal of advancing metabolism-based therapies toward first-in-disease clinical application.
Key Publications
1. Chowdhury NN, Mitchell DK, Kangro K, Eldridge K, Abrahams S, Ferraresso F, Juang LJ, Gampala S, Brewster K, Revenko A, Kastrup C, Territo PR, Clapp DW, Wang J, Belgodere JA, Saeed O, Choi SR, Han B, Wolberg AS, Cao S, Zhang C, Flick MJ, Fishel ML. Depletion of Fibrinogen Suppresses Growth of Primary Tumors and Metastasis of Pancreatic Ductal Adenocarcinoma. Gastroenterology. 2025 Dec 23; doi: 10.1053/j.gastro.2025.09.024. PubMed PMID: 41432649.
2. Mitchell DK, Brewster K, Makri SC, Khan J, Albright EA, Horvai A, Mang H, Lu Q, Dixon SAH, White E, Saadatzadeh MR, Bijangi-Vishehsaraei K, Gampala S, Hickey BE, Leffew H, Li X, Jiang L, Ciesielski MD, Bessler WK, Collier CD, Cohen-Gadol A, Fishel ML, Pratilas CA, Pollok KE, Angus SP, Rhodes S, Clapp W. DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures. Clin Cancer Res. 2025 May 15; 31(10):1988-2009. doi: 10.1158/1078-0432.CCR-24-3029. PMID: 40063513.
3. Gampala S, Moon HR, Wireman R, Peil J, Kiran S, Mitchell DK, Brewster K, Mang H, Masters A, Bach C, Smith-Kinnamen W, Doud EH, Rai R, Mosley AL, Quinney SK, Clapp DW, Hamdouchi C, Wikel J, Zhang C, Han B, Georgiadis MM, Kelley MR, Fishel ML. New Ref-1/APE1 targeted inhibitors demonstrating improved potency for clinical applications in multiple cancer types. Pharmacol Res. 2024 Mar;201:107092. doi: 10.1016/j.phrs.2024.107092. Epub 2024 Feb 2. PMID: 38311014.
4. Gampala S, Shah F, Lu X, Moon HR, Babb O, Umesh Ganesh N, Sandusky G, Hulsey E, Armstrong L, Mosely AL, Han B, Ivan M, Yeh JJ, Kelley MR, Zhang C, Fishel ML. Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: exploiting this novel finding as a potential target. J Exp Clin Cancer Res. 2021 Aug 10;40(1):251. PMID: 34376225
5. Gampala, S., Shah F, Zhang C, Rhodes SD, Babb O, Grimard M, Wireman RS, Rad E, Calver B, Bai RY, Staedtke V, Hulsey EL, Saadatzadeh MR, Pollok KE, Tong Y, Smith AE, Clapp DW, Tee AR, Kelley MR, Fishel ML. Exploring transcriptional regulators Ref-1 and STAT3 as therapeutic targets in malignant peripheral nerve sheath tumours. Br J Cancer. 2021 Apr;124(9):1566-1580. PMID: 33658640
| Year | Degree | Institution |
|---|---|---|
| 2017 | PhD | Indian Institute of Technology |
| 2009 | M.Sc. | Bangalore University |
| 2007 | BSC | Andhra University |
My research is centered on targeting tumor intrinsic and extrinsic metabolism to overcome therapeutic resistance in pediatric and adult solid tumors, with a primary focus on MPNST and pancreatic cancer.
Specific research interests include:
1. Tumor metabolic rewiring and redox signaling-
Defining how redox-regulated transcriptional programs, including Ref-1/APE1–dependent signaling, drive metabolic adaptation and stress tolerance in aggressive cancers.
2. Glutamine, mitochondrial, and nucleotide metabolism-
Identifying tumor dependencies on glutaminolysis, oxidative phosphorylation, and pyrimidine biosynthesis and leveraging these pathways for rational combination therapies.
3. Metabolic regulation of the tumor immune microenvironment-
Elucidating how tumor-intrinsic metabolic programs shape immune suppression, immune evasion, and therapeutic response.
4. Preclinical therapeutic development and biomarker discovery-
Using patient-derived models, syngeneic systems, and genetically engineered mouse models to evaluate metabolic inhibitors and define pharmacodynamic and predictive biomarkers.
5. Translational strategies for NF1-associated malignancies-
Developing dual-metabolic therapeutic approaches for NF1-driven MPNST with the goal of translation to clinic.