Email

timothyp@bcm.edu

Positions

Chair/Professor

Biochemistry and Molecular Pharmacology
Baylor College of Medicine
Houston, TX US

Cullen Trust for Higher Education Academic Chair

Baylor College of Medicine
Houston, Texas United States

Addresses

Department of Pharmacology (Office)

Room: BCMN-N520.1
Houston, TX 77030
United States

Education

BS from Creighton University

05/1983 - Omaha, Nebraska United States

Biology

PhD from University Of Iowa

04/1988 - Iowa City, Iowa United States

Genetics

Post-Doctoral Fellowship at Stanford University

01/1991 - Stanford, California United States

Honors & Awards

Award for Beta-lactamase Research

E.P. Abraham (01/2009)

Endowed Chair, The Cullen Trust for Higher Education Academic Chair

Baylor College of Medicine (07/2007)

Fellow

American Academy of Microbiology (01/2002)

MERIT Award

National Institutes of Allergy and Infectious Diseases, National Institutes of Health (01/2001)

Best Overall Course Award for BCM Graduate School Core Curriculum for Molecular Methods course.

Baylor College of Medicine (06/1998)

Divisional Lecturer

Division A Lecture

American Society for Microbiology (01/1997)

Excellence in Graduate Education Award

Baylor College of Medicine, Department of Microbiology and Immunology (06/1996)

ICAAC Young Investigator Award

(ICAAC, Interscience Conference on Antimicrobial Agents and Chemotherapy)

American Society for Microbiology (01/1994)

Young Investigator Award

American Society for Microbiology Vector Laboratories (01/1994)

Professional Interests

• Protein structure/function and functional genomics
• Enzymology
• Structural Biology
• Membrane Proteins
• Drug Resistance Mechanisms
• Drug Discovery and Medicinal Chemistry

Websites

Selected Publications

• Sun, Z., Hu, L., Sankaran, B., Prasad, B.V.V., and Palzkill, T. "Differential active site requirements for NDM-1 β-Lactamase hydrolysis of carbapenem versus penicillin and cephalosporin antibiotics.." Nat. Commun.. 2018;9:4524.
• Lu, S., Hu, L., Lin, H., Judge, A., Rivera, P., Palaniappan, M., Sankaran, B., Wang, J., Prasad, B.V.V., and Palzkill, T. "An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M -lactamase drug-resistance enzymes.." Nat. Commun.. 2022;13:6726.
• Moghadasi, S.A., Heilmann. E., Khalil, A., Nnabuife. C., Kearns, F., Ye, C., Moraes, S.N., Costacurta, F., Esler, M., Aihara, H., von Laer, D., Martinez-Sobrido, L., Palzkill, T., Amaro, R.E., and Harris, R. "Transmissible SARS CoV-2 variants with resistance to clinical protease inhibitors.." Sci. Adv.. 2023;9:eade8778.
• Su, L., Huang, W., Neill, F.H., Estes, M.K., Atmar, R.L., and Palzkill, T. "Mapping human norovirus antigens during infection reveals the breadth of the humoral immune response.." npj Vaccines. 2023;8:87.

Funding

Role of Beta-Lactamase Mutations in Antibiotic Resistance - #R01 AI32956-31

$386,000.00 (07/01/1992 - 12/31/2026)

Grant funding from NIH/NIAID

The goal of this proposal is to provide a quantitative understanding of how beta-lactam antibiotics traverse the catalytic pathway of KPC beta-lactamases, yielding insights necessary for the rational design of molecules that are poorly hydrolyzed as well as inhibitors of these enzymes. For this purpose, we will elaborate the mechanisms of acylation and deacylation of beta-lactams by the KPC-2 enzyme, determine the structure of substrates and intermediates with the enzyme, and utilize molecular dynamics to link kinetics and structural results and provide a molecular basis for beta-lactam hydrolysis by the KPC-2 and variant enzymes that are observed in drug-resistant clinical isolates.

Molecular dissection of Norovirus replication and pathogenesis to develop therapeutics - #P01 AI057788

$251,722.00 (08/01/2020 - 07/31/2024)

Grant funding from NIH/NIAID

(Estes, PI) (Palzkill, Core Director; Co-project director) Program project grant to develop diagnostics and therapeutics for caliciviruses. Projects in this grant include the development of new methods to detect caliciviruses. Palzkill’s role is as director of the Small Molecule and Protein Chemistry Core and co-director of the diagnostic development aspect of the program project.

Discovery of carbapenemase inhibitors using DNA-encoded chemical libraries - #RO1 AI143832-5

$315,000.00 (01/15/2019 - 12/31/2023)

Grant funding from NIH/NIAID

To identify small molecule inhibitors of the OXA-48, NDM-1, and KPC-2 carbapenemase enzymes using DNA-encoded chemical library technology. Together, these enzymes constitute the major mechanism of carbapenem resistance in Gram-negative bacteria.

Using DNA-encoded Chemical Libraries to Develop Inhibitors of the MCR-1 Colistin Resistance Enzyme - #R21 AI168780

$150,000.00 (04/25/2022 - 04/24/2024)

Grant funding from NIH/NIAID

The goal of this proposal is to use DNA-encoded chemical library technology to identify small molecule inhibitors of the colistin resistance enzyme MCR-1.