Pankaj Singh, PhD

Professor, Eppley Institute

Co-Leader, Cancer Biology Program,
Fred & Pamela Buffett Cancer Center

Courtesy Appointments:
Department of Biochemistry and Molecular Biology
Department of Genetics, Cell Biology and Anatomy
Department of Pathology and Microbiology  

Tel: 402-559-2726 (Office)
E-mail: Pankaj Singh

Currently accepting new students and trainees 

Pankaj Singh

Honors and Awards

2020            Featured external speaker at the NCI Division of Cancer Biology New Grantee Workshop
2019            Chair, DoD CDMRP PRCRP study section
2014            UNMC Distinguished Scientist Award
2013            UNMC Outstanding New Investigator Award
2013            Breast Cancer Idea Award from the Department of Defense
2013            Pancreatic Cancer Action Network-AACR Career Development Award
2012            Outstanding Performance Award from Eppley Institute for Research in Cancer
2010            Pancreatic cancer SPORE Career Development Award
2007            Harris Cancer Research Award
2007            Thomas Jefferson Ingenuity Award

Research Interests

Research Summary

Our laboratory has broad interests in the metabolic regulations that support tumor growth, help the tumor cells and cancer stem cells survive under harsh conditions, facilitate metastasis, and impart resistance to chemotherapies. Additionally, we are interested in determining the metabolic interrelationship of pancreatic cancer cells with their surrounding stromal and immune microenvironment and overall systemic metabolic alterations in the host that result in a poor quality of life in pancreatic cancer patients. For basic and translational research, we utilize molecular biology tools, LC-MS/MS-based metabolomics, proteomics, single-cell RNA-seq, CRISPR/Cas9 technology, genome-wide genetic and chemical library screens, cell-based assays, and animal models.

A major project in the lab aims to determine the metabolic interrelationship of pancreatic cancer cells with their surrounding microenvironment. Tumor cells exchange various metabolites with stromal cells. The metabolic crosstalk can modulate the activity of a number of immune cell types in the tumor microenvironment. Thus, we are investigating the metabolic regulation of key immune players in the tumor microenvironment. Additionally, the fibrotic stroma has been shown to protect and nourish the tumor cells and impart therapy resistance by impeding drug delivery. We are currently investigating how the tumor cells protect the stromal cells, facilitate desmoplasia, and induce pro-tumorigenic immune modulation.

Tumor cells display metabolic alterations that impact every aspect of tumor cell biology and its interaction with the tumor microenvironment. Enhanced aerobic glycolysis and metabolite flux into biosynthetic reactions in tumor cells facilitate tumor-stromal metabolite crosstalk and tumor aggressiveness. MUC1 overexpression is associated with aggressive (invasive and metastatic) forms of pancreatic and other cancers. Our studies demonstrate that MUC1 expressing pancreatic adenocarcinoma cells take up more glucose and secrete more lactate than the control cells. We also identified a number of key metabolic genes whose promoter elements are physically occupied, and the expression is enhanced by MUC1. Our studies demonstrate that MUC1 also regulates the stability and the transcriptional activity of hypoxia-inducible factor-1 alpha (HIF-1 α), the master regulator of metabolism in cancer. Our results indicate that MUC1 physically interacts with HIF-1α and its co-activator p300 and increases the recruitment of HIF-1α and p300 onto glycolytic gene promoters. Furthermore, MUC1 also stabilizes HIF-1α protein by reducing the intracellular levels of alpha-ketoglutarate. MUC1-mediated regulation of HIF-1α facilitates metabolic flux into nucleotide biosynthesis, thus outcompeting nucleotide analog-based therapies through molecular competition. Importantly, MUC1 is overexpressed by most pancreatic tumors, and hence, MUC1-induced tumor-stromal metabolic crosstalk could be targeted for suppressing the growth and invasiveness and improving therapy responsiveness in pancreatic cancer. Our long-term goal is to determine the molecular basis of metabolic alterations that facilitate invasiveness, metastasis, and poor therapy response in pancreatic cancer.

Other important projects include determining the metabolic regulation of cachexia in pancreatic cancer and the role of microRNAs in pancreatic cancer metabolism.


Selected Publications  


NIH/NCI 5P50 CA127297
Award Period: 09/23/2014-08/31/2020
Title: SPORE in Pancreatic Cancer
Role: Project Leader   

NIH/NCI 5 R01 CA210439
Award Period: 12/01/2016 – 11/30/2021
Title: Targeting the Metabolic Basis of Cachexia in Pancreatic Cancer
Role: Principal Investigator  

NIH/NCI 5 R01 CA216853 
Award Period: 03/01/2017 – 02/28/2022
Title: Metabolic Regulation of Tumor Progression, Metastasis and Chemoresistance by SIRT5/ELK3 signaling in Pancreatic Cancer 
Role: Principal Investigator

NIH/NCI 1P01CA217798 
Award Period: 06/08/2018 - 05/31/2023
Title: Pancreatic Cancer Metastasis
Role: Project Leader

NIH/NCI 2R01 CA163649  
Award Period: 09/25/2012 - 07/31/2024
Title: Targeting MUC1-induced Tumor-Stromal Metabolic Cross-talk in Pancreatic Cancer
Role: Principal Investigator