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Profiles are constructed from ORCID records, PubMed author data, and institutional affiliations via ROR. Each profile includes a MeSH-based research expertise map derived from the researcher's publication history.

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Investigator

Joseph M. Salvino

CDDT Study Section Member · National Institutes of Health, NIH Peer Review Committee

Papers

Targeting LxCxE Cleft Pocket of Retinoblastoma Protein in Immunosuppressive Macrophages Inhibits Ovarian Cancer Progression

Abstract Ovarian cancer remains a major health threat with limited treatment options available. It is characterized by an immunosuppressive tumor microenvironment (TME) maintained by tumor-associated macrophages (TAM), hindering antitumor responses and immunotherapy efficacy. In this study, we showed that targeting retinoblastoma protein (Rb) by disruption of its LxCxE cleft pocket caused preferential cell death in Rbhigh M2-polarized or M2-like Rbhigh immunosuppressive TAMs by induction of endoplasmic reticulum stress, p53, and mitochondria-related cell death pathways. A reduction of protumor immunosuppressive macrophages from TME in vivo resulted in enhanced T-cell infiltration and T-cell antitumor response and inhibited cancer progression. We demonstrated increased Rb expression in TAMs in women with ovarian cancer, which was associated with poorer prognosis. Ex vivo, we showed analogous cell death induction by therapeutic Rb targeting in TAMs in post-surgery ascites from patients with ovarian cancer. Overall, our data identify the therapeutic targeting of the Rb LxCxE cleft pocket as a promising approach for ovarian cancer treatment through depletion of immunosuppressive Rbhigh TAMs and re-shaping of the TME immune landscape.

88Works

1Papers

26Collaborators

Cell Line, TumorNeoplasmsPancreatic NeoplasmsCarcinoma, Pancreatic DuctalTumor Suppressor Protein p53Triple Negative Breast Neoplasms

Positions

2022–

CDDT Study Section Member

National Institutes of Health · NIH Peer Review Committee

2018–

Senior Editor

AACR · Cancer Research Journal

2017–

Professor Medicinal Chemistry

The Wistar Institute · Medicinal Chemistry

2017–

Scientific Director

The Wistar Institute Cancer Center · Molecular Screening Shared Resource

2011–

NIH/Small Business

NIH · Peer Review Committee

2010–

CSO

Alliance Discovery, Inc · Consulting

2019–

Peer Review committee

NIH · Probe Reports for Molecular Libraries

2019–

Special Emphasis Panel member

NIH · Peer Review Committee

2011–

Professor Medicinal Chemistry

Drexel University · Department of Pharmacology and Physiology

2010–

Adjunct Professor Medicinal Chemistry

Drexel University · Department of Pharmacology and Physiology

2010–

Vice President

AstaTech, Inc · Medicinal Chemistry Business Development

2008–

Pilot Scale Libraries (PSL)

NIH · Peer Review Committee

2004–

Director Hit-to-Lead and Computational Chemistry

Cephalon, Inc · Medicinal Chemistry

2002–

Senior Director

Rib-X Pharmaceuticals · Medicinal Chemistry

2000–

Director

Adolor Corporation · Combinatorial Chemistry Department

1999–

Department Director-Research Advisor

Rhone Poulenc Rorer (RPR) · Lead Discovery

1998–

Department Manager

Rhone Poulenc Rorer (RPR) · Lead Discovery

1996–

Section Manager

Rhone Poulenc Rorer (RPR) · Lead Discovery

1995–

Research Fellow

Rhone Poulenc Rorer (RPR) · Lead Discovery

1994–

Senior Leadership

3-Dimensional Pharmaceuticals, Inc. · Medicinal Chemistry

1989–

Senior Research Investigator

Sterling Winthrop Pharmaceutical Research Division · Medicinal Chemistry

Education

1989

Postdoctoral Fellow

University of Pennsylvania · Organic Chemistry

1987

Other training

E. I. du Pont de Nemours and Company · Life Sciences

1987

PhD

Brown University · Chemistry

1982

Master of Science

Bucknell University · Organic Chemistry

1980

bachelor of Science

Kutztown University · Chemistry

Links & IDs

0000-0002-2184-5980