Phd in LIFE SCIENCE

email: Pankaj.Trivedi@uniroma1.it
phone: 0649918250

NAME: Pankaj Trivedi
POSITION TITLE: Professor of Laboratory Medicine
EDUCATION/TRAINING
B.Sc. (Microbiology) 1983, Sardar Patel University, VV Nagar, India.
M.Sc. (Microbiology) 1985, Sardar Patel University, VV Nagar, India
Ph.D. (Tumor Immunology), 1995, Karolinska Institute, Stockholm, Sweden
Senior Research associate, 1995-1998, Neuromed Institute, Pozzilli
Senior Research associate, 1998-2001, Department of Experimental Medicine, Sapienza University, Rome

A. Personal Statement
My lab has pioneered various aspects of how EBV affects cellular proliferation and lymphoma development. Over the last few years, post-transcriptional gene regulation in virus associated cancers by microRNAs has captured our interest. We have asked how EBV encoded latent proteins influence expression of cellular microRNAs. The viral nuclear antigen EBNA2 is essential for the capacity of EBV to transform B cells. My lab was the first to show that EBNA2 can simultaneously upregulate an oncomiR miR-21 and downregulate an oncosuppressor miR, miR-146a.
Broadly, my main area of interest has been how a common and highly oncogenic virus like EBV evades immune system and in doing so turns the infected cells into cancer cells. One of the goals of my research team is to understand how EBV infected lymphoma cells escape immune surveillance by altering immune checkpoints through subversion of cellular microRNAs. Recently, we have shown that EBV encoded EBNA2 can downregulate miR-34a to upregulate PD-L1. Our latest findings show that the same viral protein also negatively affects ICOSL by an increase in miR-24. Our ultimate aim is to use 3D microfluidic chip based tumor immunogenicity evaluation microfluidic system (TIEMS) to stratify lymphoma patients for immune checkpoint blocking therapies. Using these biomimetic platforms and autologous tumor-T cell culture, we would like to evaluate and reconstitute tumor immunogenicity by combining miRNAs and IC blockers.

B. Positions and Honors
Positions and Employment
2020-present - Full Professor, Dept. Exp. Medicine, Sapienza University of Rome, Italy
2001-2020 - Associate Professor, Dept. Exp. Medicine, Sapienza University of Rome, Italy
1999-2001 - Recipient of a fellowship from the Italian Cancer Society (AIRC).
1998 - Pasteur Institute, International Network, Rome, Italy, Fellowship
1996-1999 - Italian National Health Institute (Istituto superior di Sanità) Fellowship
1992-1995 - Karolinska Institute Education Fellowship (Utbildningsbidrag)
1986-1991 - Cancer research Institute New York and Concern Foundation Los Angeles, USA, fellowship at Karolinska Institute, Stockholm
1985 - University Grant commission of India Fellowship (gratefully declined)

Other Experience and Professional Memberships
2012-2019 -Board member, PhD course in Life Science, Sapienza University of Rome.
2009-present -International examiners committee, Chittaranjan National Cancer Center, Calcutta, India
2016-present -International examiner committee, Indian Institute of Technology, (IIT), Mandi and Indore, India.
2017-present -Chairman, Undergraduate course in Physiotherapy, Sapienza University of Rome, Italy.
2012-Present -Associate Editor, microRNA journal
2010-2014 -Editorial board Member, Lymphoma journal
2018 -Guest Editor, Special issue on microRNA and human diseases, International J of Mol. Sciences
2019-present -Editorial board member, Scientific Reports (Nature group)
1991-Present -Reviewer for journals: Leukemia, JVI, PNAS, EMBO, Int. J. Cancer, PLoS One, Scientific Reports, Frontiers in Immunology and several other international journals.
2001-Present -External thesis examiner for Chittaranjan National Cancer Research Center, Calcutta, India.
2013 -External Examiner, INSERM, University of Nantes, France.
2001- Present -PhD supervisor of 7 graduate students and thesis supervisor of over 15
undergraduate students, Sapienza University of Rome.
2001-present -Invited speaker and organizer of several national and international conferences on viruses and cancers.
2001-present -Reviewer of International grants like Israel Academy of Sciences, Danish Cancer Society, Dutch Cancer Society, Association for International Cancer Research, UK, Food and Health Bureau of the Government of the Hong Kong Special administrative region, People's Republic of China, Maturation and Accelerating Translation With INdustry, MATWIN, French Cancéropôles network, France

Patent:
2018 -International Patent: RNA aided immunotherapeutics. Inventors: Anastasiadou, Slack (Harvard) and Trivedi (Sapienza)
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019232160

Visiting faculty
2001 Visiting Professor, Hokkaido University Medical School, Sapporo, Japan.
2017 Visiting Professor, UICC Fellow, BIDMC, Harvard Medical School, Boston, USA

C. Contributions to Science
1. Establishment of a murine model to investigate immunogenicity of viral proteins: During my doctoral studies at Karolinska Institute, I established a syngeneic murine model system to evaluate immunogenicity of EBV encoded latent proteins. I was the first to show that the EBNA1, a viral protein present in all EBV infected cells is non-immunogenic. Using the same model, I demonstrated that LMP1 which is expressed in all nasopharyngeal carcinomas has evolved to be nonimmunogenic. This explains why NPCs expressing LMP1 are not rejected in immunocompetent patients.

2. EBV and phenotypic changes in associated cancers: Another important aspect of my research is how EBV induces phenotypic changes in the infected cells which help the virus to avoid immune surveillance. My colleagues and I were the first to report how EBNA2 a virally encoded protein increases BCL2 expression in B cell lymphomas. In epithelial cell model, I also showed that E-Cadherin is downregulated by EBV encoded LMP1. I also showed that EBV infected primary effusion lymphomas (PELs) are more tumorigenic than KSHV only positive PELs.

3. EBV and cellular oncogene interaction: Together with my colleagues, I have discovered that EBV alters TCL1 oncogene when the infected cells have latency I type viral gene expression. Interestingly, we found that latency III type viral gene expression pattern has the opposite effect on TCL1 expression.

4. EBV and alteration of cellular miRNA in B cell lymphomas: My major research focus is how EBV alters cellular miRNAs to make the infected cells more tumorigenic. My lab has been among the first to find that two critically important proteins encoded by EBV, namely EBNA2 and LMP1 can profoundly alter cellular miRNA expression profile. We have discovered that EBNA2 can induce miR-21 and LMP1 can induce both oncogenic and tumor suppressive miRNAs and the final effect on celluar proliferation depends on the quantitative differences.

5. EBV, EBNA2 and Immune checkpoint alteration by dysregulation of miRNAs: My lab has developed a novel tumor immunogenicity test system based on 3D microfluidic chips. Our aim is to reconstitute immunogenicity by introducing those miRNAs targeting immune checkpoints and test the potential of RNA based immuntherapeutics. We have recently shown how EBV encoded EBNA2 upregulates PD-L1 and downregulates ICOSL through modulation of miRNAs. Our findings set the stage for development of RNA based immunotherapeutics, which in combination with immune checkpoint inhibiting antibodies may improve both diagnosis and prognosis of virus associated cancers.