Paola Grandi, PhD

Assistant Professor


Paola Grandi

Contact

412-648-9097

Biography

Paola Grandi, PhD, joined the Department of Neurological Surgery as an assistant professor in April of 2005. She has a joint appointment in the Department of Microbiology and Molecular Genetics.

Dr. Grandi received a bachelor degree in biology from University of Ferrara in 1996 and her master’s degree in genetics in 1997. She earned a PhD in biochemistry from the University of Ferrara in 2001. In 2001 Dr. Grandi received a fellowship for U.S. study from University of Ferrara and was a post-doctoral fellow from 2001-2005 in the Molecular Neurogenetics Department at the Massachusetts General Hospital.

Dr. Grandi is a member of the American Society of Gene Therapy and American Association Cancer Research and is the assistant editor of the journal Gene Therapy. She is considered to be a scientific leader in the field of immuno-oncology and oncolytic vectors.

Dr. Grandi built her scientific career by developing innovative approaches to treat solid tumors focusing on gliomas. She established her independence in the department where she created an engineered oncolytic HSV vector armed with novel payload combinations that altered the Extracellular Matrix (ECM) and the Tumor Microenvironment (TME) in a manner to promote the development of anti-tumor immunity.

Dr. Grandi received NIH funding for her research as an independent investigator. This work resulted in several important publications and two patents related to vector design and performance. These are the first oHSV vectors in which vector safety relied on differential expression of miRNA in tumor versus normal brain cells rather than vector mutations. These advances in vector design and anti-tumor activity provided the core technologies that led to the establishment of Oncorus Inc., a start-up oncolytic virus company in Cambridge in 2016. Dr. Grandi has been recently invited by the Society of Neuroscience to lead the educational session on oncolytic vector and gene therapy for neurodegenerative diseases.

Specialized Areas of Interest

Gene therapy for brain tumors using HSV-based vectors; molecular targeting to tumor cells; molecular mechanisms of tumor cell migration and the role of miRNAs in cancer progression; extracellular matrix (ECM).

Professional Organization Membership

American Society of Gene and Cell Therapy
American Association of Cancer Research
Society for Neuroimmunology
International Society for Stem Cell Research

Education & Training

BS, Biology, University of Ferrara, 1996
MSc, Genetics, University of Ferrara, 1997
PhD, Biochemistry, University of Ferrara, 2001

Honors & Awards

University of Pittsburgh Innovation Award, 2018
15 Fiercebiotech, 2016
Scientist of the Month, March, American Society for Gene and Cell Therapy, 2012

Selected Publications

Choudhury SR, Hudry E, Maguire CA, Sena-Esteves M, Breakefield XO, Grandi P. Viral vectors for therapy of neurologic diseases. Neuropharmacology  [Epub ahead of print], 2016.

Nakashima H, Kaufmann JK, Wang PY, Nguyen T, Speranza MC, Kasai K, Okemoto K, Otsuki A, Nakano I, Fernandez S, Goins WF, Grandi P, Glorioso JC, Lawler S, Cripe TP, Chiocca EA. Histone deacetylase 6 inhibition enhances oncolytic viral replication in glioma. J Clin Invest 125(11):4269-80, 2015.

Mazzacurati L, Marzulli M, Reinhart B, Miyagawa Y, Goins WF, Li A, Kaur B, Caligiuri M, Cripe T, Chiocca N, Amankulor N, Cohen JB, Glorioso JC, Grandi P. Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV. Mol Ther 23(1):99-107, 2015.

Uchida H, Chan J, Shrivastava I, Reinhart B, Grandi P, Glorioso JC, Cohen JB. Novel mutations in gB and gH circumvent the requirement of known gD Receptors in herpes Simplex Virus 1 Entry and cell-to-cell spread. J Virol 87(3):1430-42, 2013.

Grandi P, Fernandez J, Szentirmai O, Carter R, Gianni D, Sena-Esteves M, Breakefield XO. Targeting HSV-1 virions for specific binding to epidermal growth factor receptor-vIII-bearing tumor cells. Gene Ther 17(9):655-63, 2010.

Uchida H, Chan J, Goins WF, Grandi P, Kumagai I. Cohen JB, and Glorioso, JC. A double mutation in glycoprotein B compensates for ineffective gD-dependent initiation of herpes simplex virus type 1 infection. J Virol 84(23):12200-9, 2010.

Hong CS, Fellows W, Niranjan A, Alber S, Watkins S, Cohen JB, Glorioso JC, Grandi P. Ectopic matrix metalloproteinase-9 expression in human brain tumor cells enhances oncolytic HSV vector infection. Gene Ther 17(10):1200-5, 2010.

Frampton AR Jr, Uchida H, von Einem J, Goins WF, Grandi P, Cohen JB, Osterrieder N, Glorioso JC. Equine herpesvirus type 1 (EHV-1) utilizes microtubules, dynein, and ROCK1 to productively infect cells. Vet Microbiol 141(1-2):12-21, 2010.

Grandi P, Peruzzi P, Reinhart B, Cohen JB, Chiocca EA, Glorioso JC. Design and application of oncolytic HSV vectors for glioblastoma therapy. Expert Rev Neurother 9(4):505-17, 2009.

Uchida H, Shah WA, Ozuer A, Frampton AR Jr, Goins WF, Grandi P, Cohen JB, Glorioso JC. Generation of herpesvirus entry mediator (HVEM)-restricted herpes simplex virus type 1 mutant viruses: resistance of HVEM-expressing cells and identification of mutations that rescue nectin-1 recognition. J Virol 83(7):2951-61, 2009.

A complete list of Dr. Grandi's publications can be reviewed through the National Library of Medicine's publication database.