Shelli R. McAlpine, Ph.D.
Associate Professor
Organic synthesis of natural products and bioorganic chemistry
Office: CSL 208
Office Phone: 619-594-5580
e-mail: mcalpine_at_sciences.sdsu.edu
Curriculum Vita
- 1987-1991 B.S. U of Illinois Champaign/Urbana. Research with Prof Eric N. Jacobsen
- 1991-1993 Research Associate Merck Pharmaceuticals
- 1993-1997 Ph.D. UCLA Organic chemistry
- 1997-2000 Post-doc at Harvard University with Professor Stuart Schreiber
- 2000-2006 Assistant Professor at San Diego State University
- 2006- Current Associate Professor at San Diego State University
McAlpine Group Page | McAlpine Research Projects
Research Interests
We are currently working on four organic synthesis projects, and three biology projects, where the synthetic compounds made in each project are linked to biological assays required for understanding their mechanism and cytotoxicity. We were recently awarded a large grant from the Frasch Foundation, as well as grants from several other agencies. As such we are actively recruiting students. We are looking for both synthetic chemists and biology students to do research in our group. Since January 2006 we have published nine papers on three synthetic projects, and have two more papers submitted for publication in January 2008. These publications contain biological assay data generated by our research group. The synthesis in our group varies from making peptidomimetics using sulfer ylides, KAHA ligation chemistry, and click chemistry to the synthesis of complex natural products based on large marcrocycles. The biology experiments run in our group range from basic cytotoxicity assays on up to 18 cell lines (including colon, pancreatic, lung, breast, and prostate), to mechanistic assays involving apoptosis, pull-down, RNAi, and western blot assays. Thus, our group offers the unique opportunity to do synthetic chemistry, biology, or both.
We have published 16 papers since my lab started at SDSU in 2001, and we currently have three patent applications. We have presented our work extensively in the community, I have given 46 invited seminars since starting at SDSU and my students have presented 55 posters at meetings around the world (including presentations in Australia, England, and ShangHai!). I expect my students to present at least once at a national or international meeting and to publish an average of three papers.
Being an associate, tenured professor, I have established a full-fledged research program in organic synthesis, and have initiated biological assays on the compounds we synthesize. Via my developed research program we plan to maintain publishing with the same frequency as we have accomplished this year (four manuscripts were published in 2006, five in 2007, and two already submitted in 2008). I work with my students so that they typically publish one paper/year. Thus, I feel the community knows our work, which helps my students find jobs, enter graduate programs, and find post-doc positions. Among my most recent students to graduate, two students had five publications, another graduated with four, and two others graduated with two papers. My masters’ students typically graduate with a minimum of two papers but often three, and I expect PhD students to graduate with a minimum of five papers, with a current PhD student having 10 publications to date. Thus, we are a relatively productive group. In addition, we raise money (~$1,050,000 to date) to fund students in research (a total of ~69 fellowships), as well as travel funds for meetings. We currently have funding or have been funded by: the Frasch Foundation, NIH, CSUPERB, Pfizer, Boehringer-Ingelhiem, MIRT, and the Howell Foundation. We have close ties to a number of local biotechnology companies, including Johnson and Johnson, Vertex, Neurocrine, and Ligand. My students have been very successful in obtaining positions in a multitude of places including: Ph.D. programs in organic chemistry at UCI, UCSB, UPenn, Scripps, and the prestigious Ph.D. program at NIH-oxford university (accepts 6 student out of ~1000 applicants). In addition they have successfully obtained jobs after their degrees as synthetic organic chemists at local biotech companies including: Pfizer-La Jolla, Johnson and Johnson, Merck, Neurocrine, and Ligand.
We have a diverse research program that ranges from synthesizing compounds to running biological assays. We encourage all students with interests ranging from organic synthesis to biology to explore the diversity of our projects and recognize the skills you will develop in our research group. We are interested in recruiting both synthetically oriented students as well as biology students. Currently, three of the four organic chemistry projects focus on synthesizing macrocyclic natural products, which make excellent synthetic targets for establishing structure-activity relationships (SAR) on a given biological target. These natural product Macrocycles are often viable drug candidates, and their potency in numerous therapeutic areas have long been established (C & E News March 14, 2005). There are currently 720 peptides that are drugs on the market or in some stage of clinical trials, and they are successfully used in the therapeutic areas of antibiotics, immunosuppressants, and as anticancer agents. Shown below are the structures being synthesized in our lab.
Selected Publications
- 23) Rodrigo Rodriguez, Chung-Mao Pan, William Disman, Po-Shen Pan, Robert Vasko, and Shelli R. McAlpine* "Structure-activity of Sansalvamide A derivatives and their mechanism of action in pancreatic cancer cell lines," submitted, 2008.
- 22) Erinprit Singh, Suchitra Ravula, Chung-Mao Pan, Po-Shen Pan, Robert C. Vasko, Stephanie Lapera, Sujith, Mary Kay Pflum and Shelli R. McAlpine* "Synthesis and biological evaluation of Histone Deactylase inhibitors that are based on the FR235222 scaffold," submitted, 2008.
- 21) Melinda R. Davis, Thomas J. Styers, Rodrigo A. Rodriguez, Po-Shen Pan, Robert C. Vasko, and Shelli R. McAlpine* "Synthesis and cytotoxicity of a new class of potent decapeptides macrocycles," Org Lett. In press Dec, 2007.
- 20) Katerina Otrubova, Gerald H. Lushington, David Vander Velde, Kathleen L. McGuire, and Shelli R. McAlpine* A comprehensive study of Sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines," J. Med Chem in press Dec, 2007.
- 19) Po-Shen Pan, Kathleen L. McGuire, and Shelli R. McAlpine* Identification of compounds potent against pancreatic cancer cell lines," Bio. Org. Med. Chem. Lett., v17, p5072, 2007.
- 18) Katerina Otrubova, Kathleen L. McGuire and Shelli R. McAlpine* "A scaffold targeting drug-resistant colon cancers," J. Med Chem, v50, p1999-2002 2007.
- 17) Rodrigo Rodriguez, Po-Shen Pan, Chung-Mao Pan, Suchitra Ravula, Stephanie Lapera, Erin Singh, Thomas J. Styers, Joseph D. Brown, Julia Cajica, Emily Parry, Katerina Otrubova, and Shelli R. McAlpine* "Synthesis of second generation Sansalvamide A derivatives: Novel Templates as Potent Anti-tumor Agents," J. Org. Chem. v72, p1980-2002 2007.
- 16) Thomas J. Styers, Ahmet Kekec, Rodrigo Rodriguez, Joseph D. Brown, Julia Cajica, Chris L. Carroll, Po-Shen Pan, Irene Medina, Ricardo Corral, Jennifer V. C. Johnston, Emily Parry, Stephanie Lapera, Katerina Otrubova, Kathleen L. McGuire,* and Shelli R. McAlpine* "Synthesis of Sansalvamide A derivatives and their cytotoxicity in colon cancer cell line HT-29," Bioorganic and Medicinal Chemistry, v14, p5625-5631 , 2006.
- 15) Po-Shen Pan, Fiona A. Curtis, Chris L. Carroll, Irene Medina, Lisa A. Liotta, Gary J. Sharples, and Shelli R. McAlpine*, “Novel Antibiotics: C-2 symmetrical macrocycles affecting Holliday Junction DNA processing,” Bioorganic and Medicinal Chemistry,v14, p4731-4739, 2006.
- 14) Katerina Otrubova, Thomas J. Styers, Po-Shen Pan, Rodrigo Rodriguez, Kathleen L. McGuire,* and Shelli R. McAlpine*, “"Synthesis and novel structure-activity relationships of potent Sansalvamide A derivatives,” Chemical Communications p1033-1034, 2006.
- 13) Thomas J. Styers, Rodrigo Rodriguez, Po-Shen Pan, and Shelli R. McAlpine*, “"Synthesis of novel Sansalvamide A Derivatives via new, high yielding macrocyclization conditions,” Tetrahedron Letters, v47, p515-517, 2006.
- 12) Shelli R. McAlpine, "Life as an academic: being a female assistant professor in chemistry," American Chemical Society book: Gladly We Teach, p59 August 2005.
- 11) Chris L. Carroll, Jennifer V. C. Johnston, Ahmet Kekec, Joseph D. Brown, Emily Parry, Julia Cajica, Irene Medina, Kristina M. Cook, Ricardo Corrall, Po-Shen Pan, Ricardo Corral, and Shelli R. McAlpine* “"Synthesis and cytotoxicity of novel Sansalvamide A derivatives,” Organic Letters, v7, p3481-3484 2005.
- 10) Lisa A. Liotta, Irene Medina, Jennifer L. Robinson, Chris L. Carroll, Po-Shen Pan, Ricardo Corral, Jennifer V. C. Johnston, Kristina M. Cook, Fiona A. Curtis, Gary J. Sharples, and Shelli R. McAlpine* “Novel antibiotics: Second generation macrocyclic peptides designed to trap Holliday Junctions,” Tetrahedron Letters, v45, p8447-8450 2004.