In February, Joseph Salvino, Ph.D., joined The Wistar Institute as professor in the Molecular and Cellular Oncogenesis Program and Scientific Director of the Institute’s Molecular Screening Facility. Salvino focuses on drug discovery and development and using small molecules as tools to confirm whether a newly discovered therapeutic target is “druggable.” Salvino recently answered some questions about his background in medicinal chemistry and what projects he’ll be working on at Wistar.
Q: How did you get interested in medicinal chemistry?
A: Initially, I thought I was going to pursue a career in biology, but that all changed once I took organic chemistry in college. From that moment on, I knew I wanted to design molecules that are biologically active, meaning they have beneficial effects on cells. Having a better understanding of chemistry allows me to find the proper molecules that will act on therapeutic targets. After I received my Ph.D. from Brown University in organic chemistry, I completed postdoctoral training in synthetic and medicinal chemistry at the University of Pennsylvania. The field offers tremendous flexibility as well. In my career, I’ve worked on drug design projects in a variety of disease types. I may not have a deep understanding of disease quite like biologists do, but what I’ve been able to do is take their findings and determine how to design a drug that can be tested clinically.
Q: Why do you feel Wistar is a good fit for your skills?
A: I came to Wistar from Drexel, so I’m already pretty familiar with the Philadelphia life sciences community. I’ve also had the pleasure of working with a few of Wistar’s scientists prior to coming here. For example, I’ve collaborated with Drs. Paul Lieberman and Troy Messick of Wistar’s Gene Expression and Regulation Program on their Epstein-Barr virus drug development project since 2012. At Wistar, you have so many really talented cancer biologists that have discovered several targets for a variety of diseases. From my end, I need to take those targets and make them druggable. In some cases, these scientists have the therapeutic target they want to study but are overwhelmed by the process of determining which drugs could act on that target. In other instances, the target is already druggable, but the design needs to be improved in order to reduce toxicity of the drug, which can cause adverse affects in patients. The goal is to demonstrate the effectiveness of these targets and drugs here so that we can more quickly move them into clinical trials.
Q: What are some of the projects you’ll be working on at Wistar?
A: There are several ongoing projects that I’m excited to work on. Dr. Qihong Huang is working on an exciting target called GABRA3, which is expressed in metastatic breast cancer tissue. Dr. Maureen Murphy has a great target called HSP70, a stress-survival protein found in many different types of tumors. Dr. Meenhard Herlyn’s lab is also working on a drug development project for melanoma. These are just a few examples of the types of projects I’ll be focusing on as I take these targets off the hands of the biologists and help them reach their full potential.
Q: One of your other roles here is as scientific director of Wistar’s Molecular Screening Facility. What are your plans for this facility?
A: One of the things I’m hoping to work on with our scientists is to move their discoveries into what’s known as the hit-to-lead stage. The idea is to take a target and to use something called high throughput screening to find promising lead compounds that could be studied as potential drugs. High throughput screening allows scientists to test hundreds, thousands, or many, many more compounds for biochemical activity, saving considerable time in taking these promising targets and finding the drugs that act upon them. I have enough experience to look at the structure of a molecule and, in many cases, I’ll know whether there are drugs available that may act on it. In any event, the screening helps get these discoveries to that crucial hit-to-lead stage, which ultimately results in new drugs being developed more quickly and more effectively.