New Investigator of the Month
Who are the faces of ASGCT?
ASGCT's New Investigator of the Month profiles an ASGCT member who is new to the field or just beginning an independent position. To be considered for a future New Investigator of the Month, applicants must be an Active or Associate Member of the Society. Active Members must be 10 or fewer years out from their first active, independent position.
Please click here to apply or nominate a colleague. New Investigators of the Month are selected by the ASGCT Website Taskforce.
Matthew L. Hirsch, PhD
Degrees: BA, West Virginia University; PhD, West Virginia University
Current Position: Research Associate at University of North Carolina at Chapel Hill, Gene Therapy Center
Questionnaire
Briefly describe your current research interests.
I am interested in the ability to control and exploit human DNA repair mechanisms for therapeutic purposes such as ex vivo gene correction or in vivo episomal genetic engineering.
Briefly describe how you reached your current position (educational background).
Optimistically, by guided drift. I started out in an E. coli genetics lab and transitioned to human genetics, with a side of disease therapy, for my post-doctoral program.
When and why did you first develop an interest in gene and cell therapies?
Initially, I was very interested in AAV as an efficient method of DNA transfer in human cells. Then, my therapy focus developed the first time I met with Dr. Jude Samulski.
What do you view as your greatest scientific achievement to date?
We developed a novel method of inter-molecular recombination to genetically engineer episomes from distinct transduced viral genomes using homologous oligonucleotides (a process we termed “OAGR” for Oligo-Assisted AAV Genome Recombination). In addition to discovering DNA repair biases previously reported in bacteria and yeast, OAGR also has therapeutic applications for AAV-mediated large gene therapy.
Paola Grandi, PhD
Degrees: PhD, University of Ferrara, Italy
Current Position: Assistant Professor at University of Pittsburgh
Questionnaire
Briefly describe your current research interests.
My research is focused on the development of novel oncolytic Herpes Simplex Virus-based vectors useful in the treatment of recurrent malignant glioblastoma, a form of cancer with a very poor prognosis. Oncolytic HSV vectors (oHSV) have shown promise for treatment of preclinical models of glioblastoma multiforme (GBM), and early phase human clinical trials in patients with recurrent malignant GBM have demonstrated vector safety with some evidence of efficacy. My research effort are focused on improving the oncolytic activity of replication competent HSV vectors by overcoming impediments that remain to achieving efficient tumor killing. These include (i) lack of effective vector targeting to tumor cells, (ii) inadequate intra-tumoral virus growth; (iii) reduced vector distribution due to poor initial penetration of the tumor mass and limited spread of new virions (iv) tumor cell migration from surgically resected tumor margins (v) the effect of innate immune responses that inhibit virus replication.
Briefly describe how you reached your current position (educational background).
I received a bachelor degree in Biology from University of Ferrara in 1996 and my master’s degree in Genetics in 1997. I earned a PhD in biochemistry from the University of Ferrara in 2001. In 2001 I received a fellowship for U.S. study from University of Ferrara and I was a post-doctoral fellow from 2001-2005 in the Molecular Neurogenetics Department at the Massachusetts General Hospital. I joined the Department of Neurological Surgery at the University of Pittsburgh School of Medicine as an assistant professor in April of 2005 and I have a joint appointment in the Department of Microbiology and Molecular Genetics.
When and why did you first develop an interest in gene and cell therapies?
During my PhD program in Italy, I began working on the development of new techniques to engineer HSV-based vector glycoproteins that lead to thinking about clinical applications of these engineered viruses. I decided to move to the United States as a post-doctoral fellow in the laboratory of Professor Xandra Breakefield at the Massachusetts General Hospital, where Dr. Robert Martuza had just completed the first clinical trial for GBM using oncolytic vectors based on HSV. Even though the clinical trial proved that HSV vectors are safe, it also showed that the efficacy was limited. During my studies in Dr. Breakefield’s lab I tried to answer this question: how may I improve the oncolytic activity of HSV vectors? My project was to find new strategies to improve viral spreading of the oncolytic vectors without affecting tumor cell migration. The strategy was to modify the tumor extracellular matrix to permit greater intratumoral vector distribution. This strategy was coupled with the redesign of vector specificity to allow exclusive infection of targeted tumors. In Pittsburgh I am now developing this class of new oncolytic vector whose design takes advantage of consistent differences in the expression of certain micro (mi)RNAs between normal neurons and tumor cells as a means to control the highly hierarchical progression of HSV lytic gene expression. This additional approach may increase vector safety.
What do you view as your greatest scientific achievement to date?
I think my most important achievement has been the development of insights into enhanced oncolytic vector growth and spread in glioblastomas.
Paloma H. Giangrande, PhD
Current Position: Assistant Professor at University of Iowa
Questionnaire
Briefly describe your current research interests.
The majority of the work in my laboratory focuses on membrane proteins and molecular events that occur at the plasma membrane during states of aberrant growth (cancer and cardiovascular disease). Specifically, the laboratory develops RNA-based tools (RNA aptamers and siRNAs) that serve two purposes: 1) to elucidate signaling pathways that regulate pathological proliferation and promote cell survival and 2) to modulate these cells for therapeutic intervention.
Briefly describe how you reached your current position (educational background).
I obtained my PhD in Pharmacology and Cancer Biology at Duke University where I focused on elucidating the functional roles of the progesterone receptor (PR) isoforms. Following my PhD degree in 1999, I trained as a postdoctoral fellow in the laboratory of Dr. Joseph Nevins at Duke University from 2000-2004. During this time, I focused on understanding how individual members of the E2F family of transcription factors control the regulation of target genes. After my post-doctoral training, I joined the Department of Surgery and the Center of Translational Research at Duke as a Research Assistant Professor. During this time, I focused on translating basic mechanistic insights that govern deregulated cell-growth into developing effective therapies in the setting of cancer and cardiovascular disease (intimal hyperplasia). In 2007, I was hired as an Assistant Professor in the Department of Internal Medicine at the University of Iowa.
When and why did you first develop an interest in gene and cell therapies?
During my postdoctoral training, I sought to understand how individual members of the E2F family of transcription factors control the regulation of specific target genes. At the time, very little was known about E2F-specific cofactors and, more importantly, about the differential arrangement of the various E2F transcription factors on DNA. I was the first to demonstrate that distinct E2F isoforms regulate different subsets of genes. Because these proteins are “master regulators” of the cell cycle and the E2F pathway is often deregulated in many human diseases, my work provided critical molecular insights into the cell-type specific activity of the various E2F isoforms. I wanted to apply this knowledge of fundamental mechanism of gene regulation to develop safe and effective therapies against human diseases. I thus joined Dr. Sullenger’s group at Duke University to develop E2F-specific RNA inhibitors for the treatment of intimal hyperplasia following vascular injury.
What do you view as your greatest scientific achievement to date?
My group developed a simple, all-RNA approach that utilizes a synthetic RNA ligand (aptamer) to selectively target and deliver cytotoxic small interfering RNAs (siRNAs) to specific cell types in vivo. This approach promises to reduce unintended effects that may result from non-specific delivery as well as reduce the amount of siRNA needed for therapeutic purposes, thus reducing the cost of therapy.
Melissa A. Badding
Degrees: BS, Rochester Institute of Technology, MS in Toxicology, University of Rochester
Current Position: Graduate student at University of Rochester Medical Center
Questionnaire
Briefly describe your current research interests.
Our lab studies non-viral gene delivery using naked plasmid DNA, and I am interested in examining how cytoplasmic factors can impact plasmid movement to the nucleus during gene transfer.
Briefly describe how you reached your current position (educational background).
The summer following graduation from college, I started my first rotation at URMC within the Toxicology department. I am now in my fourth year of graduate studies, working in a pulmonary gene therapy lab, and hope to complete my thesis within the next year to year and a half.
When and why did you first develop an interest in gene and cell therapies?
During my first year of graduate school I rotated in David Dean’s lab, working on plasmid DNA-microtubule interactions, and became very interested in understanding the process of gene transfer as a therapeutic approach. I have been working on this project for the last three years and it continues to fascinate me!
What do you view as your greatest scientific achievement to date?
I received the Excellence in Research Award at ASGCT's 13th Annual Meeting in 2010, and had the opportunity to present my work at the conference, which was very rewarding.
Renier J. Brentjens, MD, PhD
Degrees: BA (History), Davidson College, NC; MD, State University of New York at Buffalo, NY; PhD (Microbiology/Immunology) State University of New York at Buffalo, NY.
Current Position: Assistant Member, Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Questionnaire
Briefly describe your current research interests.
My laboratory is focused on the development of technologies related to generating patient derived T cells genetically modified, through retroviral introduction of artificial T cell receptors, termed chimeric antigen receptors (CARs), specific to tumor associated antigens. The resulting ex vivo generated T cells, now specific to tumor, are re-infused back into patients to mediate a desired anti-tumor effect. To date we have validated this approach in pre-clinical tumor models, and more recently have translated this approach into patients with B cell malignancies including acute and chronic B cell leukemias as well as B cell lymphomas using T cells genetically targeted to the CD19 antigen expressed on these tumors. Further we have expanded this program to investigate CARs targeted to the MUC16 antigen expressed on most ovarian cancers. Finally, we are currently investigating additional gene modifications whereby these targeted T cells may overcome inhibition by the immune-suppressive tumor microenvironment in pre-clinical tumor models.
Briefly describe how you reached your current position (educational background). I obtained a BA degree in history from Davidson College, NC, fully intending to go to medical school. I joined the MSTP program at SUNY Buffalo obtaining my MD degree as well as a PhD in Microbioloy/Immunology. Subsequently, I completed an Internal Medicine residency at Yale-New Haven Hospital (CT) followed by a followship in Medical Oncology at Memorial Sloan Kettering Cancer Center (NY). Upon completion of my fellowship training I was hired by MSKCC as an attending physician on the leukemia service and soon thereafter became a principle investigator of my own laboratory at the center.
When and why did you first develop an interest in gene and cell therapies?
My initial interest in gene therapy was ironically stimulated by a key note address from French Anderson at the annual ASM meeting wherein he presented initial results from the first gene therapy trial in ADA deficient pediatric patients. This talk, along with Dr Anderson’s predicted applications of this technology to the field of cancer therapy spurred my interest in gene therapy for cancer. Subsequently, during my fellowship, I sought out projects utilizing gene transfer and immune-based therapies, which in turn brought my attention to the concept of gene modifying a patient’s own T cells to recognize and kill their tumors.
What do you view as your greatest scientific achievement to date?
Translation of pre-clinical findings to the clinical setting is a difficult process. To this end, I see my greatest scientific achievement to date as the combined pre-clinical establishment that CD19 targeted T cells can eradicate established CD19+ tumors in mice, and the subsequent lengthy and arduous process of translating these findings to the clinical setting in the form of several currently ongoing clinical trials treating chemotherapy refractory B cell cancers with gene modified autologous CD19 targeted T cells.