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Rajani K. Ravi, Ph.D.

Photo of Dr. Rajani K. Ravi, Ph.D.
  • Assistant Professor of Otolaryngology - Head and Neck Surgery

Background

Dr. Rajani Ravi received her Ph.D. from Andhra University in India.

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Titles

  • Assistant Professor of Otolaryngology - Head and Neck Surgery
  • Assistant Professor of Oncology

Departments / Divisions

Centers & Institutes

Education

Degrees

  • Ph.D., Andhra University (India) (1982)

Research & Publications

Research Summary

Working collaboratively with Dr. Atul Bedi in a translational cancer research program, our objective is to provide fundamental insights into the molecular determinants and mechanisms by which tumor cells evade death signals entrained by the immune system and anticancer agents.  We have developed novel bifunctional immunostimulatory antibody-ligand traps (Y-traps- aPDL1-TGFβRII, aCTLA4-TGFβ RII, and EGFR- TGFβ RII) to counteract tumor immune tolerance and to enhance the efficacy of head and neck cancer immunotherapy.

The program demonstrates the immune system’s instrumental role in the in vivo antitumor efficacy of cytotoxic chemotherapeutic agents and tumor-targeted antibodies. Our studies show that the tumor cell-autonomous expression of transforming growth factor-β (TGFβ) is a key molecular determinant of the de novo or acquired resistance of cancers. Our studies further exhibit that TGFβ and checkpoint inhibitors (PDL1 or CTLA-4) function as cooperative brakes on the immune system. The Y-traps we have developed simultaneously abrogate TGFβ mediated resistance, thereby providing an effective immunotherapeutic strategy against cancers that are resistant to immune checkpoint inhibitors.

Selected Publications

View all on Pubmed

Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev. 2000 Jan 1; 14(1):34-44. PubMed PMID: 10640274; PubMed Central PMCID: PMC316350

Ravi R, Bedi GC, Engstrom LW, Zeng Q, Mookerjee B, Gélinas C, Fuchs EJ, Bedi A. Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB. Nat Cell Biol. 2001 Apr;3(4):409-16. doi: 10.1038/35070096. PubMed PMID: 11283615

Ravi R, Jain AJ, Schulick RD, Pham V, Prouser TS, Allen H, Mayer EG, Yu H, Pardoll DM, Ashkenazi A, Bedi A. Elimination of hepatic metastases of colon cancer cells via p53-independent cross-talk between irinotecan and Apo2 ligand/TRAIL. Cancer Res. 2004 Dec 15; 64(24):9105-14. doi: 10.1158/0008-5472.CAN-04-2488. PubMed PMID: 15604280

Ravi R, Noonan KA, Pham V, Bedi R, Zhavoronkov A, Ozerov IV, Makarev E, V Artemov A, Wysocki PT, Mehra R, Nimmagadda S, Marchionni L, Sidransky D, Borrello IM, Izumchenko E, Bedi A. Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy. Nat Commun. 2018 Feb 21; 9(1):741. doi: 10.1038/s41467-017-02696-6. PubMed PMID: 29467463; PubMed Central PMCID: PMC5821872

Patents

Compositions and Methods for Targeted Immunomodulatory Antibodies and Fusion Proteins
Patent # US Patent: 9,850,306 | 12/26/2017

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-.beta.)) and regulatory T cells and/or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

Compositions and Methods for Targeted Immunomodulatory Antibodies and Fusion Proteins
Patent # EP2542590 | 03/31/2017

Compositions and methods for targeted immunomodulatory antibodies and fusion proteins (EGFR-TGFBRII)
Patent # US Patent: 9441044 | 09/13/2016

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-.beta.)) and regulatory T cells and/or immunosuppressive myeloid dendritic cells (DCs). By conteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

Compositions and Methods for Targeted Immunomodulatory Antibodies and Fusion Proteins (CTLA4-TGFBRII)
Patent # US Patent: 8993524 | 03/31/2015

https://assignment.uspto.gov/patent/index.html#/patent/search/resultAssignment?id=29136-898

Compositions and Methods for Targeted Immunomodulatory Antibodies and Fusion Proteins
Patent # JP2013521311 | 11/08/2018

https://worldwide.espacenet.com/publicationDetails/claims?CC=JP&NR=2013521311A&KC=A&FT=D&ND=2&date=20130610&DB=&locale=#

Compositions and Methods for Targeted Immunomodulatory Antibodies and Fusion Proteins
Patent # US Patent: 10442860 | 10/15/2019

Contact for Research Inquiries

Phone: 443-287-7491

Activities & Honors

Memberships

  • American Association for Cancer Research, 2000
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