Sridhar Hannenhalli, Ph.D.

Sridhar Hannenhalli, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Cancer Data Science Laboratory


Cancer is characterized by major transcriptional and epigenetic changes not only in the cancer cells but also in other cell types that jointly constitute the tumor microenvironment (TME). The cancer phenotype is ultimately a result of dynamically changing interactions between various cell types. While much of the focus of research in oncogenesis, metastasis, drug resistance and relapse has been on protein-coding mutations, a growing body of literature clearly points to an alternate mechanism centered on transcription heterogeneity and cellular plasticity that sets the stage for oncogenesis. Broadly, cancers hijack several developmental and homeostatic processes for proliferation, immune evasion, and therapy resistance. Precise molecular links between cancer and the developmental/homeostatic processes is of great interest. As mentioned above, while most of the focus has been on the protein-coding mutations, a vast majority of mutations and germline variation fall in the non-coding portion of genome, however, identifying the functional subset of such non-coding variations and mutations has been challenging due to lack of appropriate models.  Further complicating functional investigation of cancers is that the very notion of a gene’s or a cell’s function may be highly context-specific and the knowledge of context-specific functions is highly incomplete. The research in Hannenhalli lab is broadly focused on Cancer Gene Regulation, and is organized into four broad areas: (1) Transcriptional heterogeneity, cellular plasticity, and regulatory mechanisms underlying oncogenesis, metastasis, and therapy response, (2) Developmental and homeostatic origins of cancer, (3) Development of deep learning models to identify functional non-coding polymorphisms and mutations underlying cancer, and (4) Intrinsic and extrinsic context-specific functionality of genes and cells, and 

We are a purely dry lab with expertise in computational and statistical methods, machine learning, and analysis of a variety of high-throughput omics data. We strongly believe in team science and welcome collaborations.

Areas of Expertise

Single Cell Omics
Transcriptional Regulation


Selected Key Publications

De novo human brain enhancers created by single-nucleotide mutations

Shan Li, Sridhar Hannenhalli, Ivan Ovcharenko
Sc Advances. 2023.
Full-Text Article
[ Journal Article ]

Broad misappropriation of developmental splicing profile by cancer in multiple organs

Arashdeep Singh, Arati Rajeevan, Vishaka Gopalan, Piyush Agrawal, Chi-Ping Day, Sridhar Hannenhalli
Nat Comm. 2022.
Full-Text Article
[ Journal Article ]

A transcriptionally distinct subpopulation of healthy acinar cells exhibit features of pancreatic progenitors and pancreatic ductal adenocarcinoma

Vishaka Gopalan, Arashdeep Singh, Farid Rashidi Mehrabadi, Li Wang, Eytan Ruppin, H. Efsun Arda and Sridhar Hannenhalli
Cancer Research. 2021.
Full-Text Article
[ Journal Article ]

Beyond Synthetic Lethality: Charting the Landscape of Pairwise Gene Expression States Associated with Survival in Cancer

Magen A, Das Sahu A, Lee JS, Sharmin M, Lugo A, Gutkind JS, Schäffer AA, Ruppin E, Hannenhalli S
Cell Reports. 28(4): 938-948, 2019.
Full-Text Article
[ Journal Article ]

Bayesian integration of genetics and epigenetics detects causal regulatory SNPs underlying expression variability

Avinash Das, Michael Morley, Christine Moravec, WH Wilson Tang, Hakon Hakonarson, MAGNet Consortium, Kenneth B. Margulies, Thomas P. Cappola, Shane Jensen, and Sridhar Hannenhalli.
Nat Commun. 6: 8555, 2015. [ Journal Article ]

Job Vacancies

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Postdoctoral Fellow (Visiting)
Piyush Agrawal, Ph.D.
Postdoctoral Fellow (Visiting)
Arashdeep Singh, Ph.D.
Postdoctoral Fellow (Visiting)
Vishaka Datta Sreenivasa Gopalan, Ph.D.
PreDoctoral Fellow (CRTA)
Arvind Jaya Shankar
Cole Ruoff
Mahfuza Sharmin


Sep 2023.     Piyush Agrawal wins FARE award

October 2023.    Omar Sikder moves to FDA as Data Scientist

August 2023.    Gulden Olgun moves to Hacettepe University as Asst Professor of Computer Science

Fall 2022.    Arati Rajeevan moves to Stanford for grad school

Fall 2020.     Annan Timon moves to U Penn for grad school