James S. Nowick

Picture of James S. Nowick
Distinguished Professor, Chemistry
School of Physical Sciences
PH.D., Massachusetts Institute of Technology, 1990
A.B., 1985, Columbia University
Phone: (949) 824-6091
Fax: (949) 824-9920
Email: jsnowick@uci.edu
University of California, Irvine
4126 Natural Sciences 1
Mail Code: 2025
Irvine, CA 92697
Research Interests
Organic and Bioorganic Chemistry, Chemical Biology
NSF Postdoctoral Fellow, M. I. T.

Joined UCI faculty in 1991
Research Abstract

Research in the Nowick group focuses on the chemistry and biology of peptides. Areas of particular interest include understanding molecular basis of amyloid diseases, such as Alzheimer’s disease, and the development of new antibiotics.

The design, synthesis, and study of new molecules is central to our efforts. We use small molecule chemical synthesis, peptide synthesis, and protein expression to create the molecules that we study, and molecular modeling, NMR spectroscopy, and X-ray crystallography to gain insights into their structures and biomolecular interactions. Experiments with mammalian cells and bacteria, as well as fluorescence microscopy help elucidate the biological properties of the molecules that we create, as do some animal-based studies in mice. A particular area of interesting our laboratory is the structures and supramolecular interactions of ß-sheets, which are central to the folding and assembly of the peptides associated with amyloid diseases, such as Alzheimer’s disease, as well as the antibiotic teixobactin.

Our extensive program of research on understanding the molecular basis of amyloid diseases focuses on developing chemical models of the toxic amyloid oligomers associated Alzheimer’s disease and other amyloid diseases. In typical studies, we design peptides derived from Aß and other amyloidogenic peptides and proteins and then study their structures and assembly, as well as their biological properties. Through X-ray crystallography, we have been able to observe the structures of a variety oligomers formed by constrained ß-hairpin peptides derived from key amyloidogenic peptides and proteins. Current efforts seek to correlate these chemical models of amyloid oligomers with biogenic amyloid oligomers found in the brain and to develop antibodies and vaccines to block the neurodegeneration associated with these amyloid oligomers.

In 2015 we became interested in the newly reported antibiotic teixobactin and launched a program of study to learn more about its chemistry and biology. By synthesizing teixobactin analogues and studying their antibiotic activity, we gained new insights into the mechanism of action of teixobactin. Through X-ray crystallography, we discovered that teixobactin forms dimers and higher-order assemblies through ß-sheet formation that can bind to its molecular targets on the cell membrane of Gram-positive bacteria. We are now using what we have learned from teixobactin to design new antibiotics against MRSA, VRE, and other dangerous pathogens.

Students in the Nowick group partake fully of the rich environment of mentorship and training provided by our research laboratory. Graduate students participate in hypothesis generation, data collection, data analysis, and communication through oral and written presentation. Many graduate students choose to mentor undergraduate research students, further enhancing their graduate training while helping to train the next generation. I meet with students individually each week to discuss their results and plans for subsequent experiments. Additional scheduled and ad-hoc meetings occur throughout the week. When students are writing papers for publication, I work closely with them, providing guidance and feedback in the writing process.

My group and I meet collectively on Tuesday afternoons during our weekly group meetings. Our group meetings consist of three formats: research, literature, and workshop. In our research group meetings, students present and discuss their results orally with slides and get feedback and discussion that leads to ideas for future experiments. In our literature group meetings, we discuss important publications from the current literature, with each student making slide presentations on articles. When students are preparing to give talks or engaging in various writing projects, the group often provides feedback and guidance in a workshop format. Through this program of research training, continuing education, and mentorship, students acquire the skills to become successful independent scientists.

Group members are encouraged to partake of the rich educational and networking opportunities provided by attending and presenting at scientific meetings. The annual Peptide Therapeutics Symposium in San Diego provides great opportunities to present and network with scientists from the nearby pharmaceutical and biotechnology industries in San Diego. The biennial Chemistry and Biology of Peptides Gordon Research Conference in Ventura is also superb. Other popular meetings include the biennial American Peptide Symposium, the biennial National Organic Symposium, and the biannual meetings of the American Chemical Society. For group members who present, I try to help cover part of the costs of attending these and other scientific meetings.

Ph.D. graduates from the Nowick group go on to careers in the pharmaceutical and biotechnology industries and academia, as well as non-traditional pathways. Positions of Nowick group alumni include careers at Roche, GSK, Encodia, and other leading companies, as well as faculty positions at NYU, the University of South Carolina, and Orange Coast College. I am happy to provide Ph.D. graduates continued mentorship and networking opportunities throughout their careers, and I encourage group alumni to check in periodically by e-mail, phone, Zoom, or in person.

Nowick Group Website

Other Affiliations
Chao Family Comprehensive Cancer Center (UCI)
Institute for Genomics and Bioinformatics (UCI)
Alzheimer's Disease Research Center, UCI MIND (UCI)

Course Video Lectures on YouTube
Chem 203. Organic Spectroscopy, Fall 2020
Chem 203. Organic Spectroscopy, Fall 2020 Course Website
Chem 203. Organic Spectroscopy, Fall 2011
Chem 125. Advanced Organic Chemistry
Chem 51A. Organic Chemistry
Chem 51B. Organic Chemistry (Professor David Van Vranken)
Chem 51C. Organic Chemistry
Links to other OpenChemistry Lecture Videos

Scholarly Websites
Organic Spectroscopy Problems

Link to The UCI Chemistry Outreach Program Web Page

Available Technologies
Awards and Honors
•Charles R. Bennett Service Through Chemistry Award from the ACS Orange County Section
•American Chemical Society (ACS) Fellow
•American Association for the Advancement of Science (AAAS) Fellow
•NOGLSTP Scientist of the Year Award
•UCI School of Physical Sciences Award for Outstanding Contributions to Undergraduate Education
•American Chemical Society Arthur C. Cope Scholar Award
•UCI Chancellor's Award for Excellence in Undergraduate Research
•Alfred P. Sloan Research Fellowship
•Camille Dreyfus Teacher-Scholar Award
•Presidential Faculty Fellow
•UCI Award for Outstanding Faculty Contribution to Undergraduate Research
•Arnold and Mabel Beckman Foundation Young Investigator
•National Science Foundation Young Investigator
•American Cancer Society Junior Faculty Research Award
•Camille and Henry Dreyfus Foundation Distinguished New Faculty Award
•National Science Foundation Postdoctoral Fellow
•American Chemical Society Division of Organic Chemistry Graduate Fellow
•National Science Foundation Graduate Fellow
Short Biography
James Nowick received his Bachelors degree in Chemistry in 1985 from Columbia University and his Ph.D. degree in Organic Chemistry in 1990 from MIT, where he was both an NSF Graduate Fellow and an ACS Division of Organic Chemistry Graduate Fellow. After an NSF postdoctoral fellowship in supramolecular chemistry at MIT, he began his independent career as an Assistant Professor at UCI in 1991. He was promoted to Associate Professor in 1996 and Professor in 1998. Professor Nowick served as Chair of the Department of Chemistry from 2016-2019. He is currently a Distinguished Professor in the Department of Chemistry and the Department of Pharmaceutical Sciences.

Professor Nowick’s research interests include bioorganic chemistry and chemical biology; molecular recognition and supramolecular chemistry; and peptide and protein structure. Current efforts in his research laboratory are focused on understanding the molecular basis of Alzheimer's disease and other amyloid diseases and the development of antibiotics.

With his group members, Professor Nowick has published more than 120 research publications to date. In recognition of his scientific contributions, he has received a Camille and Henry Dreyfus Foundation New Faculty Award, an American Cancer Society Junior Faculty Research Award, an NSF Young Investigator Award, an Arnold and Mabel Beckman Foundation Young Investigator Award, a Presidential Faculty Fellow Award, a Camille Dreyfus Teacher-Scholar Award, an Alfred P. Sloan Research Fellowship, and an American Chemical Society Arthur C. Cope Scholar Award. He is a Fellow of the American Association for the Advancement of Science and the American Chemical Society. For his contributions to research and education at UCI, he has received the Award for Outstanding Faculty Contribution to Undergraduate Research, the Chancellor's Award for Excellence in Undergraduate Research, and the School of Physical Sciences Award for Outstanding Contributions to Undergraduate Education.
(Selected Publications)

"An Improved Turn Structure for Inducing ß-Hairpin Formation in Peptides" Li, X.; Sabol, A. L.; Wierzbicki, M.; Salveson, P. J.; Nowick, J. S. Angew. Chem. Int. Ed. 2021, 60, 22776-22782.
"Phenylalanine Mutation to Cyclohexylalanine Facilitates Triangular Trimer Formation by ß-Hairpins Derived from Aß" Haerianardakani, S.; Kreutzer, A. G.; Salveson, P.; Samdin, T. D.; Guaglianone, G. E.; Nowick, J. S. J. Am. Chem. Soc. 2020, 142, 20708-20716.
"A Fluorescent Teixobactin Analogue" Morris, M. A.; Malek, M.; Hashemian, M. H.; Nguyen, B. T.; Manuse S.; Lewis, K.; Nowick, J. S ACS Chem. Biol. 2020, 15, 1222-1231.
"Design, Synthesis, and Study of Lactam and Ring-Expanded Analogues of Teixobactin" Yang, H; Pishenko, A. V.; Li, X.; Nowick, J. S. J. Org. Chem. 2020, 85, 1331-1339.
"X-ray Crystallographic Structure of a Teixobactin Derivative Reveals Amyloid-like Assembly" Yang, H; Wierzbicki, M.; Du Bois, D. R.; Nowick, J. S. J. Am. Chem. Soc. 2018, 140, 14028-14032.
"Stabilization, Assembly, and Toxicity of Trimers Derived from Aß" Kreutzer, A. G.; Yoo, S.; Spencer, R. K.; Nowick, J. S. J. Am. Chem. Soc 2017, 139, 966-975.
"Elucidation of the Teixobactin Pharmacophore" Yang, H.; Chen, K. H.; Nowick, J. S. ACS Chem. Biol. 2016, 11, 1823-1826.
"X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aß17-36 ß-Hairpin" Kreutzer, A. G.; Hamza, I. L.; Spencer, R. K.; Nowick, J. S. J. Am. Chem. Soc. 2016, 138, 4634-4642.
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