Miller, Students Present at ACS
2 October 2014 Miller, Students Present at ACS
Associate Professor of Chemistry Justin Miller and students Steffi Cramer 15, Janae Garofalo 15 and Grace Hutton 16 presented a poster at the American Chemical Society (ACS) national meeting held in San Francisco this summer. The poster was titled, Spiruchostatin A and potential anticancer analogs via a latent thioester solid-phase route, and the research is a continuation of work Miller has been doing for 10 years. Greg Shelkey 14 was also a co-author on the study but was unable to attend.
Five years ago, Miller and student researchers published on the synthesis of Spiruchostatin A, a natural product that inhibits an enzyme that is sometimes partially responsible for carcinogenesis. Over the past five years, the Miller group, along with students in Intermediate Organic Chemistry, synthesized a number of analogs-potential anticancer chemotherapeutics structurally similar to the natural products. Leila Peraro 13 and Xiaoyu (Janice) Zang 13 were instrumental in developing this methodology, which Cramer, Garofalo, Hutton and Shelkey used to synthesize a synthetic molecule thats more active than the natural product. This means it kills cancer cells at a lower concentration than is required of the natural product. It is possible that it may also target the appropriate protein more specifically. The hope is that it can be used to treat cancer with fewer side effects.
Our goal is to create molecules specific enough that they only do what we want them to and not a whole lot else. Its a like trying to hit a nail into wood with a hammer instead of with a sledgehammer, says Miller. Were trying to find just the right size hammer.
In Millers laboratory, they create and test the analogs and expect them to perform a certain way. Professor of Biology Sigrid Carle and Associate Professor of Biology Patricia Mowery then conduct research to determine whether the analogs are effective in killing cancer cells, and also what they do on a cellular level whether it is the right size hammer, per se. While not specifically presented at the ACS conference, this collaborative work is part of a National Science Foundation funded project. It combines cell biology with organic chemistry in an interdisciplinary program designed by HWS faculty to seek and characterize possible anticancer therapies.
This unique project allows undergraduate students to discover what it is like to work in a real drug discovery process better preparing them as scientists for graduate school, laboratory work and future endeavors.
At the conference, Miller, Cramer, Garofalo and Hutton reported on the synthesis of the molecules what they did, how and why and what can be learned from it. Feedback was positive for their development of the method for making the molecule, which Miller notes is significant.
My undergraduates were in the same arena as people who have graduate and postdoc students working 12 hours a day with better equipment. We have to think about problems in a way that allows us to handle it given the resources and available time in the lab, and we came up with a clever solution, he says.
He added that his students participated readily in, and benefited from, the intellectual exchange at the conference -and even leading up to it. Garofalo discussed a reaction that is part of the experiment with an ACS member on the plane en route to the event. The group has now tried the approach that her fellow passenger suggested, and it looks as if it will work.
Miller adds, Its the collective experience of the other presenters and attendees at the poster session that we were hoping to mine-and we were successful.
Also while in San Francisco, Miller and current students met up with alums who are now chemistry graduate students, including Zang 13, now at Stanford, and Wade Perkins 12, currently at UC Berkeley.
Photo: Xiaoyu (Janice) Zang 13, Grace Hutton 16, Wade Perkins 12, Janae Garofalo 15, and Steffi Cramer 15 gather on Hobart Street in San Francisco.