Name: Roodolph P. St Pierre

 

CURE Year:

Summer 2010

Summer 2011 

Education and Degree(s):

UMASS Boston, Boston MA -B.S. in Chemistry

Harvard University, Cambridge MA -Chemical Biology Program, PhD Candidate

PhD advisor: Cigall Kadoch, PhD

Describe your current position:

I am currently a 3rd year graduate student in Chemical Biology at Harvard. I am studying the implication of chromatin remodeling deregulation in cancer. 

CURE mentor(s):

Dr. LaTese Briggs

Dr. Angela Koehler 

What was your CURE research question?:

During the summer of 2010, I worked as an intern at the Broad Institute of Harvard and MIT under the guidance of Dr. LaTese Briggs, at the time, a postdoctoral fellow in the laboratory of Dr. Stuart Schreiber. I focused on a structural biology project from which I learned to express and purify exogenous proteins in bacteria for crystallographic studies with and without small molecule docking. Additionally, these structural efforts introduced me to several important molecular biology-based tools, including the design of novel expression constructs with dual affinity tags. Our protein of interest was histone deacetylase 8 (HDAC8), a molecular target in T-cell lymphoma and neuroblastoma. HDACs belong to a family of enzymes that remove acetyl groups from the side chains of lysine residues. HDAC activity is most often correlated with transcriptional repression, and is widely deregulated (by mutation and amplifications/deletions) in cancer. We aimed to obtain a crystal structure with a newly discovered small molecule inhibitor to help understand its binding modalities, aiming to guide medicinal chemistry-based design of more potent inhibitor analogs.  Although we did not obtain crystals large enough for X-ray diffraction, these studies using different HDAC8 domains did help move forward a series of more potent small molecules based on Thermoshift binding assays that made use of our batches of pure protein.   

Memorable CURE Experience:

My most memorable CURE experience was my first oral presentation that took place during summer 2010. It was by far the most daunting presentation I had ever given at the time. I remember practicing my talk over a dozen times the night before, worrying that I was going to botch the presentation. Once I was past the first three introductory slides, I delved into data mode and started noticing a few heads nodding in approval; suddenly all the dread and doubt dissipitated and gave way to a sense of personal historic accomplishment. My first CURE talk actually convinced me that I could have a career in the sciences. Up until summer 2010, I never thought that I could command a stage, deliver a science talk and convey results of my findings in a clear manner that made sense to an audience. 

How did CURE help you get to where you are today?:

CURE was instrumental in my pursuit of cancer research. CURE provided various auxiliary skills that are crucial for success in a research environment. For instance, the journal club sessions that took place during the year taught me how to approach a scientific paper to extract relevant information. Our journal club facilitators would encourage us to talk and challenge our understanding of the material. Toward the end, we would critique the paper and most importantly address the issues the data failed to address. It was eye-opening to realize that all papers were question-generators as opposed to a rigid text meant to be the be-all and end-all. I learned that scientific advancement was painfully slow, deliberate and extremely well-controlled. Furthermore, the redundancy in publishing was meant to serve as internal controls for scientist at large to further validate one’s findings before they were immortalized in text books. Every step of the way, be it the journal clubs, the conferences I was able to attend thanks to the data I was able to generate, the symposiums and the scientific outings, CURE gave me the confidence and courage to tackle the next step.    

Favorite place to eat in the Longwood Medical Area when you were a CURE student:

Il Mundo Pizzeria on Huntington street.

What is your current five year plan?:

At the moment, I am contemplating a postdoctoral stint at the intersection of chromatin remodeling biology and cancer. Turns out, subunits of the mSWI/SNF complex (a chromatin remodeler) are mutated in more than 20% of cancers from various tissue types. We have yet to understand how all these mutations lead to tumorigenesis. I see myself tackling this quintessential “how” in various cancers, which will help advance novel therapeutics for countless suffering from neoplasms with no cures in sight.  

If I weren’t a (current position), I’d be:

I’d be most likely pursuing different avenues to reach my (current position). I love what I do and can’t fathom doing anything else. Pushing the boundaries of knowledge is a thrill like no other. I doubt any other field of study would be as personally fulfilling.