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Pharmacology and Molecular Sciences
on studying the intricate chemical changes in proteins that change how they behave in a cell
Recently, faculty members in Pharmacology won an NIH Pioneer Award and multiple awards from the American Chemical Society. How does it feel to be chair of this all-star department?
COLE: My sense is that many departments at Hopkins have similar high-quality faculty. Mainly I try to stay out of my faculty members’ way and let them do their research, but I try to take care of them when they need things to make sure that they reach their potential. We have a very collaborative, collegial environment that is important for supporting and nurturing each other.
What is your favorite part of the job?
COLE: I’m really proud and excited to be working with my phenomenally bright, hardworking and talented students and postdocs. I get a lot of satisfaction seeing them succeed. Some of my lab members have become professors or captains of industry.
What kind of research do you do?
COLE: If there is a common thread in our lab, it’s that we study a lot of the chemical changes that can happen to proteins. We study how these changes affect the protein’s activity in the cell and whether those changes may be modified with a drug that can lead to a clinical benefit.
The other focus of our lab is designing our own chemical structures that can bind to a protein of interest and modify its activity in some way. We design these compounds to get into cells and be useful at least as pharmacological tools in a laboratory for studying the function and behavior of a protein. But, ultimately we hope that this work can lead to the design of safe and effective drugs that are useful therapeutics.
What kinds of proteins do you study?
COLE: One protein that we study is LSD1 (lysine specific demethylase 1) that removes chemical methyl groups from proteins, the effect of which turns genes on and off. Interestingly, LSD1 is very similar to monoamine oxidase, the enzyme targeted by an early class of psychiatry drugs from the 1950s--MAOIs. Some of these antidepressant drugs prevent LSD1 from working too. We are exploring whether the MAOIs and other similar compounds work by changing which genes are turned on and whether this mechanism of gene control can be used to target other diseases, like cancer.
Another protein we study is p300, which regulates many other proteins by attaching chemical acetyl groups to them. It wears many hats and is involved in cancer, metabolism and glucose control. I am very enthusiastic about this protein’s medical applications. As a result I am a co-founder of a company called Acylin Therapeutics that is dedicated to developing drugs that bind to p300 and prevent it from working.
What do you hope your company will achieve?
COLE: We would like to develop treatments for melanoma. We’ve shown that drugs against p300 can block the growth of cancer cells. We have compounds that work reasonably well, but we’d like to make them into something better and safer that might go into patients eventually.
--Interviewed by Vanessa McMains
Philip Cole on taking advantage of the biological revolution to design new therapeutics: