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Sanjeevani Arora, PhD

Sanjeevani Arora, PhD
About

Assistant Professor

Research Program

Lab Overview

My laboratory seeks to understand how innate differences (such as germline variants) in DNA replication and/or repair impact two critical areas in precision oncology: (1) what underlies an individual’s cancer risk, and (2) how an individual will respond to cancer treatment. Currently my work focuses on colorectal and renal tumors, but results from my work are applicable to multiple tumor types. My long-term goal is to increase our understanding of DNA replication, and repair pathways and their role in colorectal and other cancers, to better predict cancer risk and reduce cancer incidence by allowing opportunities to implement cancer prevention strategies and early detection.

 
DNA damage response and repair marker (gammaH2AX) significantly segregates early-onset colorectal cancer patients from matched cancer-free controls. GammaH2AX marker was assessed in peripheral blood lymphocytes of familial early-onset colorectal cancer patients and matched controls (Figure from Arora et. al., Gastroenterology 2015).
POLE and POLD1 are the major replicative DNA polymerases. Genetic mutations in POLE and POLD1 lead to proofreading errors occur throughout the genome, causing mutagenesis, genetic instability and cancer. The cancer spectrum of POLE and POLD1 includes colorectal, endometrial and other tumors. (Figure from Nicolas et. al., Gene 2016).
Early-onset renal cancer (eoRC) patients carry germline pathogenic variants in DNA damage response and repair genes These results indicate that patients diagnosed with eoRC may benefit from undergoing comprehensive multigene panel testing that includes genes outside of the scope of those currently known to increase renal cancer risk. (Figure from Hartman et. al., Scientific Reports 2020).

Clinical

Education and Training

Educational Background

  • Postdoctoral Fellow, Fox Chase Cancer Center, Philadelphia, PA, 2017
  • PhD, University of Toledo - Health Science Campus, Toledo, OH, 2012
  • MS, CMR Institute of Management Studies, Bangalore University, Bangalore, India, 2006
  • BS, Garden City College, Bangalore University, Bangalore, Karnataka, 2004

Certifications

  • AACR Integrative Molecular Epidemiology: Bridging Cancer Biology and Precision Medicine, July 2017
  • ACMG Genomics Case Conference: "Solving the Unresolved: A systematic approach to WES Negative Patients in the Undiagnosed Diseases Network"

Memberships

  • American Association for Cancer Research (AACR), Member
  • American Society for Cell Biology (ASCB), Member
  • American Society of Human Genetics (ASHG), Member
  • Association of Women in Science (AWIS), Member
  • European Association for Cancer Research (EACR), Member
  • Fox Chase Cancer Center, Co-Founder and Leader, "Women in Science" group
  • DNA Repair and Genome Stability working group (FCCC), Founder and organizer
  • Healthcare Businesswomen’s Association (HBA), Mentoring Program Director, “Represent Manager” -Women in Science
  • Journal of Biochemical Technology, Authors Advisory Board
  • World Association of Young Scientists, Member
  • 13th Annual Midwest DNA Repair Symposium, UT-HSC, Organizing Member and Host

Honors & Awards

  • FY17 Peer Reviewed  Cancer Research Program (PRCRP) Career Development Award, 2018
  • NCI T32 training fellowship, 2016
  • Travel award for presenting at “ACMG Annual Clinical Genetics meeting” in Salt Lake City, UT, Fox Chase Cancer Center Postdoctoral program, 2015
  •  1st place- Oral presentation, 19th Annual Postdoctoral Day, Fox Chase Cancer Center, 2014
  •  "Board of Directors" Postdoctoral Fellowship, Fox Chase Cancer Center 2013

 

See Dr. Arora's profile on LinkedIn      Twitter: @sanjeevaniarora

Research Profile

Research Program

Research Interests

Cancer genetic studies to improve screening, early detection and treatment

  • Mechanisms underlying genetically undefined hereditary cancers
  • Predictive biomarkers for response to chemoradiation therapy
  • Novel strategies to screen for individuals at high-risk for cancer

Lab Overview

My laboratory seeks to understand how innate differences (such as germline variants) in DNA replication and/or repair impact two critical areas in precision oncology: (1) what underlies an individual’s cancer risk, and (2) how an individual will respond to cancer treatment. Currently my work focuses on colorectal and renal tumors, but results from my work are applicable to multiple tumor types.

In the area of cancer risk prediction, we seek to identify and functionally assess novel or rare ‘risk’ germline variants in the population. Knowing which germline variants confer risk and which don’t is important because physicians don’t know how to act upon the massive number of variants of uncertain significance that have been identified by sequencing studies. We currently are evaluating variants in replicative DNA polymerases, POLE and POLD1, as these are known to cause mutagenesis, genetic instability and cancer (such as colorectal, endometrial).

Our approach to solving the ‘too many uncertain variants’ problem is based on a novel hypothesis, that germline POLE and POLD1 variants that are dysfunctional in the tumor also have a detectable dysfunctional signature in the germline. We are leveraging big data of tumor and germline to build a Germline Signature, which can be adopted into clinical practice to guide risk prediction and allow for application of cancer prevention strategies (e.g., lifestyle interventions) or early detection (e.g. by improving cancer screening panels). Collaborating with clinical partners, we plan to improve and validate this tool in prospective studies. Longer term, we plan to use the Germline Signature to build risk prediction models.

In the area of individual response to cancer treatment, we are integrating germline variation data with biological assessment of innate capacity to repair DNA damage to develop a ‘signature’ that predicts the magnitude of benefit from chemoradiation therapy. My approach is particularly novel because tumor-specific signatures have been sought but no biomarker has ever been established; this may be because prior studies did not evaluate innate factors. This work will deliver preclinical evidence that could allow for precision stratification of patients to therapies.

Currently, my two research directions are relatively separate. But I envision they will eventually meet. By pursuing both it may be possible to identify specific innate factors that influence both risk and response to treatment. Results may elucidate mechanisms common to many cancers and/or underlying predisposition to a certain tumor type.

Lab Description

In the area of cancer risk prediction, we seek to identify and functionally assess novel or rare ‘risk’ germline variants in the population. Knowing which germline variants confer risk and which don’t is important because physicians don’t know how to act upon the massive number of variants of uncertain significance that have been identified by sequencing studies. We are evaluating genetic variants in replicative DNA polymerases, POLE and POLD1, as these are known to cause mutagenesis, genetic instability and cancer (such as colorectal, endometrial).

Our approach to solving the ‘too many variants of uncertain significance’ problem is based on a novel hypothesis, that germline POLE and POLD1 variants that are dysfunctional in the tumor also have a detectable dysfunctional signature in the germline. We are leveraging big data of tumor and germline to build a Germline Signature, which can be adopted into clinical practice to guide risk prediction and allow for application of cancer prevention strategies (e.g., lifestyle interventions) or early detection (e.g. by improving cancer screening panels). Collaborating with clinical partners, we plan to improve and validate this tool in prospective studies. Longer term, we plan to use the Germline Signature to build risk prediction models.

In the area of cancer treatment, we are investigating biomarkers of therapeutic response in rectal cancer. Neoadjuvant chemoradiation therapy (nCRT) is currently the standard treatment for locally advanced rectal cancer (clinical TNM stage II—III). Locally advanced rectal cancer accounts for ~60% of newly diagnosed patients. For many patients, nCRT has dramatically improved outcomes, but ~70-80% of patients who receive nCRT show poor or no response, and CRT is extremely toxic. Currently, there is no clinically actionable biomarker to predict which rectal cancer patients are likely to respond to nCRT. As a result, many patients are exposed to this toxic, DNA damaging therapy (radiation and chemotherapy) without benefit. Therefore, a biomarker for nCRT response would improve precision treatment, and ultimately improve survival and prevent recurrence in individual with rectal cancer.

In the area of individual response to cancer treatment, we are integrating germline variation data with biological assessment of innate capacity to repair DNA damage to develop a ‘signature’ that predicts the magnitude of benefit from chemoradiation therapy. Our approach is particularly novel because tumor-specific signatures have been sought but no biomarker has ever been established; this may be because prior studies did not evaluate innate factors. This work will deliver preclinical evidence that could allow for precision stratification of patients to therapies.

Currently, my two research directions are relatively separate. But I envision they will eventually meet. By pursuing both it may be possible to identify specific innate factors that influence both risk and response to treatment. Results may elucidate mechanisms common to many cancers and/or underlying predisposition to a certain tumor type.

Extramural Affiliations
 

  • Adjunct, Department of Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University
  • Adjunct, Department of Biochemistry & Molecular Biology, Drexel University School of Medicine
Lab Staff

Elena Demidova, MS

Graduate Student

Room: P2149
215-214-3966

Philip Czyzewicz III, BS

Scientific Technician II

Room: P2149
215-214-3964

Additional Staff

Former Personnel:

Jessica Mauricette, University of Delaware-FCCC Summer Fellow 2019
Current: Undergraduate student, University of Delaware

Randy Lesh, Alpha Omega Alpha Carolyn L. Kuckein Student Fellow 2019
Current: Medical student, Geisinger Commonwealth School of Medicine

Mercedes Davis, Drexel University Undergraduate Co-op
Current: Continuing undergraduate studies, Drexel University

Amanda Browne, NCI CURE Program Fellow
Current: Scientific Technician I, Arora Lab 

Waleed Iqbal, Master’s thesis, Drexel University School of Medicine
Current: Graduate Student, School of Biomedical Engineering Science & Health Systems, Drexel University
 

Volunteer:

Nina Shah, Summer Research Volunteer
Current: Continuing undergraduate studies, Haverford College

Publications

Selected Publications

Shah S.M., Demidova E.V., Lesh R.W., Hall M.J., Daly M.B., Meyer J.E., Edelman M.J., Arora S., Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology. Cancer Treat Rev. 104: 102337, 2022. PMC9016579 https://www.ncbi.nlm.nih.gov/pubmed/35051883.

Iqbal W., Demidova E.V., Serrao S., ValizadehAslani T., Rosen G., Arora S., Rrm2b is frequently amplified across multiple tumor types: Implications for DNA repair, cellular survival, and cancer therapy. Front Genet. 12: 628758, 2021.PMC8045241. https://www.ncbi.nlm.nih.gov/pubmed/33868369.

Hartman TR, Demidova EV, Lesh RW, Hoang L, Richardson M, Forman A, Kessler L, Speare S, Golemis EA, Hall MJ, Daly MB, Arora S*. Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer. *Corresponding. Sci Rep. 2020 Aug 11;10(1):13518. doi: 10.1038/s41598-020-70449-5. PMID: 32782288

Arora S*, Velichinskii R, Lesh RW, Usman A, Kubiak M, Bansal P, Edelman MJ, Borghaei H, and Boumber Y*. Existing and emerging biomarkers for immune checkpoint immunotherapy in solid tumors. *Co-corresponding. Adv Ther. 2019 Aug 13. doi: 10.1007/s12325-019-01051-z. [Epub ahead of print] Review. PMID: 31410780

Nicolas E., Demidova E.V., Iqbal W., Serebriiskii I.G., Vlasenkova R., Ghatalia P., Zhou Y., Rainey K., Forman A.F., Dunbrack R.L., Jr., Golemis E.A., Hall M.J., Daly M.B., Arora S., Interaction of germline variants in a family with a history of early-onset clear cell renal cell carcinoma. Mol Genet Genomic Med. 7(3): e556, 2019. PMC6418363. 9.924

Serebriiskii I.G., Connelly C., Frampton G., Newberg J., Cooke M., Miller V., Ali S., Ross J.S., Handorf E., Arora S., Lieu C., Golemis E.A., Meyer J.E., Comprehensive characterization of ras mutations in colon and rectal cancers in old and young patients. Nat Commun. 10(1): 3722, 2019. PMC6700103. 11.878

Arora S., Heyza J.R., Chalfin E.C., Ruch R.J. ,Patrick S.M., Gap junction intercellular communication positively regulates cisplatin toxicity by inducing DNA damage through bystander signaling. Cancers (Basel). 10(10)2018. PMC6210410. 6.162

Arora S., Huwe P.J., Sikder R., Shah M., Browne A.J., Lesh R., Nicolas E., Deshpande S., Hall M.J., Dunbrack R.L., Jr., Golemis E.A., Functional analysis of rare variants in mismatch repair proteins augments results from computation-based predictive methods. Cancer Biol Ther. 18(7): 519-533, 2017. PMC5639829. 2.879

Nicolas E, Golemis EA, Arora S*. POLD1: Central mediator of DNA replication and repair, and implication in cancer and other pathologies. Gene 590:128-41, 2016. Pubmed PMID: 27320729 *corresponding.

Nicolas E, Arora S, Zhou Y, Serebriiskii IG, Andrake MD, Handorf E, Bodia DL, Vockley JG, Dunbrack RL, Ross EA, Hall MJ, Golemis EA, Giri VN, and Daly MB.  Systematic evaluation of underlying defects in DNA repair as an approach to case-only assessment of familial prostate cancer. Oncotarget 6:39614-33, 2015, PubMed PMID: 26485759. PMCID: 4741850... Expand

Additional Publications

MyNCBI

Open Positions

Open Positions

About the Position

The Arora Laboratory at Fox Chase Cancer Center is hiring highly ambitious and self-motivated Postdoctoral Fellows in Cancer Genetics. The laboratory uses state-of-the-art technologies and collaborations with leading scientists and clinicians to understand how innate differences (such as germline variants) in DNA repair genes impact two critical areas in precision oncology: (1) how an individual will respond to cancer treatment, and (2) what underlies an individual’s cancer risk. Currently our work focuses on inherited colorectal and renal tumors but results from our work are applicable to multiple tumor types. The postdoctoral fellow will work with basic scientists and clinical experts with a goal to translate research findings to clinical care. The Arora laboratory seeks candidates that published peer reviewed manuscripts and that have strong expertise in cancer genetics, genomics, DNA repair mechanisms, cancer biology, bioinformatics, molecular biology, cell biology, and/or biochemistry.

Learn more about research at the Arora Laboratory.

About the Training Environment

As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for almost 90 years. We are home to excellent research facilities, top clinicians and scientists, and outstanding patient care. Our singular focus on cancer, which couples discovery science with state of the art clinical care and population health, remains the foundation of our work.

The scientist training programs at Fox Chase Cancer Center provide professional development opportunities in four core areas identified as crucial for successful careers in science, research, and health care including communication, leadership, teaching, and mentorship. Upon joining the program, graduate students and postdocs develop individual development plans to help guide their growth. Training throughout the year is supplemented with free professional development opportunities, including a robust ‘How To’ series, writing courses, networking, mentorship, and teaching opportunities, a trainee-led seminar series, a trainee-led annual Research Conference, and more. Postdocs at Fox Chase Cancer Center are supported by the Temple University Postdoc Association and the Office of Academic Affairs at Fox Chase, and are compensated with competitive pay and benefits.

In addition to the robust training program, scientists at Fox Chase Cancer Center benefit from being part of the rich scientific and biotech environment in the Philadelphia region. Many of our former trainees are now employees (and contacts) at nearby institutions and companies, including The Wistar Institute, Merk, GSK, AACR, and numerous others.

To Apply

Email a CV, cover letter describing your research interest(s) and career goals, and the names and contact information for three professional references to Sanjeevani Arora, PhD at Sanjeevani.Arora@fccc.edu

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
Learn more about Research Volunteering.

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