Lindsay R. Comstock-Ferguson

Education

B.S., 2000, Northern Arizona University
Ph.D. (Pharmaceutical Sciences), University of Wisconsin-Madison
Postdoc (Biomolecular Chemistry, J.M. Denu), University of Wisconsin-Madison

Research Description

Research in our laboratory lies at the chemistry-biology interface and seeks to gain a deeper understanding of the role of post-translational modifications in the dynamic regulation of cellular function and how alterations in these modification states correlate to disease.  The combination of organic chemistry, biochemistry, and molecular biology is utilized in developing small-molecule tools to not only identify where substrates are modified, but to investigate the physiological effect of such modifications in vivo.  Specifically, cofactor mimics of S-adenosyl-L-methionine and adenosine triphosphate bearing reactive functionalities serve as substrates for cellular methyltransferases and kinases, respectively, to generate easily-detected biological complexes.  Ultimately, the long-term value of such agents to serve as biochemical tools will allow us to begin understanding the underlying chemical driving forces which induce and alter biologically important processes and disease through post-translational modifications.

Publications

Srinivas, P, Nosrati, M, Zelinskaya, N, Dey, D, Comstock, LR, Dunham, CM, Conn, GL. 30S subunit
recognition and G1405 modification by the aminoglycoside- resistance 16S ribosomal RNA
methyltransferase RmtC. PNAS 2023;120:e2304128120.

Laughlin, ZT, Nandi, S, Dey, D, Zelinskaya, N, Witek, MA, Srinivas, P, Nguyen, HA, Kuiper, EG,
Comstock, LR, Dunham, CM, Conn, GL. 50S subunit recognition and modification by the
Mycobacterium tuberculosis ribosomal RNA methyltransferase TlyA. PNAS 2022;114:e2120352119.

Sirasunthorn, N, Jailwala, A, Gerber, A, Comstock, LR. Evaluation of N-Mustard Analogues of S-
Adenosyl-L-methionine with Eukaryotic DNA Methyltransferase 1. Chemistry Select 2019;4:10525-
10531.

Hymbaugh, SJ, Pecor, LM, Tracy, CM, Comstock, LR. Protein Arginine Methyltransferase 1-dependent
labeling and isolation of histone H4 through N-mustard analogs of S-adenosyl-L-methionine.
ChemBioChem 2019;20:379-384.

Hymbaugh Bergman, SJ, Comstock, LR. N-Mustard analogs of S-adenosyl-L-methionine as biochemical probes of protein arginine methylation. Bioorganic and Medicinal Chemistry. 2015; 23: 5050-5055.

Ramadan, M, Bremner-Hay, NK, Carlson, S, Comstock, LR. Synthesis and evaluation of N6-substituted azide- and alkyne-bearing N-mustard analogs of S-adenosyl-L-methionine. Tetrahedron. 2014; 70: 5291-5297.

Du, Y, Hendrick, CE, Frye, KS, Comstock, LR. Fluorescent DNA labeling by N-mustard analogs of S-adenosyl-L-methionine. ChemBioChem. 2012; 13: 2225-2232.

Mai, V, Comstock, LR. Synthesis of an azide-bearing N-mustard analog of S-adenosyl-L-methionine. Journal of Organic Chemistry. 2011; 76: 10319-10324.

Comstock, LR, Rajski, SR. Methyltransferase-directed DNA strand scission. Journal of the American Chemical Society. 2005;127:14136-14137.

Comstock, LR, Rajski, SR. Conversion of DNA methyltransferases into azidonucleosidyl transferases via synthetic cofactors. Nucleic Acids Research 2005; 33: 1644-1652.