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Faculty


Kathleen M. Frey

Professor, Full Time

B.S., University of Connecticut Molecular & Cell BiologyPh.D. University of Connecticut Pharmaceutical Sciences – Medicinal Chemistry

Description

Dr. Kathleen Frey joined the Division of Pharmaceutical Sciences during the Fall 2015 semester. Prior to joining the Pharmaceutical Sciences faculty at LIU, Dr. Frey was a Postdoctoral Fellow at Yale University School of Medicine in the department of Pharmacology. At Yale, Dr. Frey received a postdoctoral fellowship from the National Institute of Health to design less toxic anti-HIV agents with improved resistance profiles. In addition to designing antiviral agents, Dr. Frey has worked collaboratively with other scientists in Yale Chemistry and Pharmacology departments to identify novel drug targets for lung cancer and melanoma.

Dr. Frey gained experience in drug design, x-ray crystallography, and computational chemistry during her graduate career at the University of Connecticut School of Pharmacy. In collaboration with multidisciplinary scientists, Dr. Frey played a major role in designing novel antibacterial agents for methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus anthracis using drug-target crystal structures. She is trained as an x-ray crystallographer and conducts the majority of her data collection research at the National Synchrotron Light Source (NSLS) of Brookhaven National Laboratory. Her research interests focus on structure-based and computer-aided drug design for infectious diseases and cancer. Within 10 years of her career, Dr. Frey has authored 23 peer reviewed articles, 1 invited review, and 1 patent in the fields of medicinal chemistry, structure-based drug design, biochemistry, microbiology, and molecular pharmacology.

Specialties

Medicinal Chemistry, Molecular Pharmacology, Biochemistry, Protein X-ray Crystallography, Computational Chemistry, Drug Design

Publications

Bolstad, D.B., Bolstad, E.S., Frey, K.M., Wright, D.L., and Anderson, A.C. (2008) A structure--‐based approach to the development of potent and selective inhibitors of dihydrofolate reductase from Cryptosporidium. J Med Chem., 51: 6839--‐6852.

Beierlein, J.M., Frey, K.M., Bolstad, D.B., Pelphrey, P.P., Joska, T., Smith, A.E., Priestley, N.D., Wright, D.L., and Anderson, A.C. (2008) Synthetic and Crystallographic Studies of a New Inhibitor Series Targeting Bacillus anthracis Dihydrofolate Reductase. J Med Chem., 54: 7532-7540.

Frey, K.M., Liu, J., Lombardo, M.N., Bolstad, D.B., Smith, A.E., Priestley, N.D., Wright, D.L., and Anderson, A.C. (2009) Crystallographic     Complexes    of    Wild-type    and    Mutant    MRSA    DHFR Reveal    an    Alternate Conformation of NADPH that May be Linked to Trimethoprim Resistance. J Mol Bio., 387: 1298--‐1308.

Beierlein, J.M.,* Deshmukh, L.,* Frey, K.M.,* Vinogradova, O., and Anderson, A.C. (2009) The Solution Structure  of Bacillus  anthracis  Dihydrofolate  Reductase  Yields  Insight  into  the Analysis  of Structure Activity Relationships for Novel Inhibitors. Biochemistry., 48: 4100-4108.

Frey, K.M., Lombardo, M.N., Wright, D.L., and Anderson, A.C. (2010) Towards the Understanding of Resistance Mechanisms in Clinically Isolated Trimethoprim-resistant, Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase. J Struct Biol., 170: 93-97.

Frey, K.M.,* Georgiev, I.,* Donald, B.R., and Anderson, A.C. (2010) Predicting Resistance Mutations Using Protein Design Algorithms. Proc Natl Acad Sci USA. 107: 13707-13712.

Viswanathan, K.,* Frey, K.M.,* Scocchera, E.W., Martin, B.D., Swain III, P.W. Alverson, J., Priestley, N.D., Anderson, A.C., and Wright, D.L. (2012) Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-linked Antifolates are Potent Inhibitors of MRSA and Streptococcus pyognes. PLoS One, 7(2): e29434.

Frey, K.M., Viswanathan, K., Wright, D.L., and Anderson, A.C. (2012) Prospective Screening of Novel Antibacterial Inhibitors of Dihydrofolate Reductase for Mutational Resistance. Antimicrob Agents Chemother., 56: 3556-3562.

Kim, J., Wang, L., Li, Y., Becnel, K.D., Frey, K.M., Garforth, S.J., Prasad, V.R., Schinazi, R.F., Liotta, D.C., and Anderson, K.S. (2012) Pre-steady State Kinetic Analysis of Cyclobutyl Derivatives of 2'-deoxyadenosine 5'-triphosphate as Inhibitors of HIV-1 Reverse Transcriptase. Biorg Med Chem Lett., 22: 4064-4067.

Frey, K.M., Bollini, M., Mislak, A.C., Cisneros, J.A., Gallardo-Macias, R., Jorgensen, W.L., and Anderson, K.S. (2012) Crystal Structures of HIV-1 Reverse Transcriptase Reveal Key Interactions for Drug Design. J Am Chem Soc., 134: 19501-19503.

Bollini, M., Frey, K.M., Cisneros, J.A., Spasov, K.A., Das, K., Bauman, J.D., Arnold, E., Anderson, K.S., and Jorgensen, W.L. (2013) Extension into the Entrance Channel of HIV-1 Reverse Transcriptase – Crystallography   and Enhanced Solubility.  Biorg Med Chem Lett., 23: 5209-5212.

Kumar, V.P., Frey, K.M., Wang, Y., Jain, H.K., Gangjee, A., and Anderson, K.S. (2013) Substituted Pyrrolo[2,3-d]pyrimidines  as Cryptosporidium hominis Thymidylate Synthase Inhibitors. Biorg Med Chem Lett., 23: 5426-5428.

Iyidogan, P., Sullivan, T.J., Chordia, M., Frey, K.M., and Anderson, K.S. (2013) Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. ACS Med Chem Lett. 4: 1183-1188.

Lee, W., Gallardo-Macias, R., Frey, K.M., Spasov, K.A., Bollini, M., Anderson, K.S., and Jorgensen, W.L. (2013) Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group. J Am Chem Soc. 135: 16705-16713.

Frey, K.M.,* Gray, W.T.,* Spasov, K.A., Bollini, M., Gallardo-Macias, R., Jorgensen, W.L., and Anderson, K.S. (2014) Structure-based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV-1 Reverse Transcriptase. Chem Biol Drug Des. 83: 541-549.

Mislak, A.C., Frey, K.M., Bollini, M., Jorgensen, W.L., and Anderson, K.S., (2014). A Mechanistic and Structural Investigation of Modified Derivatives of the Diaryltriazine Class of NNRTIs Targeting HIV-1 Reverse Trancriptase. Biochim Biophys Acta. 1840: 2203-2211.

Kumar, V.P., Cisneros, J.A., Frey, K.M., Castellanos-Gonzalez, A., Wang, Y., Gangjee, A., White Jr., A.C., Jorgensen, W.L., and Anderson, K.S. (2014) Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis Thymidylate Synthase-Dihydrofolate Reductase. Biorg Med Chem Lett., 4: 4158-4161.

Lee, W., Frey, K.M., Gallardo-Macias, R., Spasov, K.A., Bollini, M., Anderson, K.S., and Jorgensen, W.L. (2014) Picomolar Inhibitors of HIV-1 Reverse Transcriptase: Design and Crystallography of Naphthyl Phenyl Ethers. ACS Med Chem Lett. 5: 1259-1262.

Reeve, S.M., Gainza, P. Frey, K.M., Georgiev, I., Donald, B.R., and Anderson, A.C. (2015). Protein Design Algorithms Predict Viable Resistance to an Experimental Antifolate. Proc Natl Acad Sci USA. 112: 749-754.

Frey, K.M., Puleo, D.E., Spasov, K.A., Bollini, M., Jorgensen, W.L. and Anderson, K.S. (2015) Structure-based Evaluation of Non-nucleoside Inhibitors with Improved Potency and Solubility that Target HIV Reverse Transcriptase Variants. J Med Chem. 58: 2737-2745.

Sohl, C.D., Ryan, M., Luo, B., Frey, K.M., and Anderson, K.S. (2015) Illuminating the molecular mechanism of tyrosine kinase inhibitor resistance for the FGFR1 gatekeeper mutation: the Achilles’ heel of targeted therapy. ACS Chem Biol. 10: 1319-1329.

Lee. W., Frey, K.M., Gallardo-Macias, R., Spasov, K.A., Chan, A.H., Anderson, K.S., and Jorgensen, W.L. (2015) Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. Biorg Med Chem Lett. 25: 4824-4827. 

Gray, W.T.*, Frey, K.M.*, Laskey, S.B., Mislak, A.C., Spasov, K.A., Lee, W.G., Bollini, M., Siliciano, R.F., Jorgensen, W.L., and Anderson, K.S. (2015) Non-nucleoside Inhibitors Active Against HIV Reverse Transcriptase with K101P, a Mutation that Confers High Level Rilpivirine Resistance. ACS Med Chem Lett. 6: 1075-1079.

* Authors contributed equally.

Patents

Anderson, A.C., Wright, D.L., Frey, K.M., Paulsen, J.L., Scocchera, E.W., Viswanathan, K. Heterocyclic Analogs of Propargyl-linked Inhibitors of     Dihydrofolate   Reductase.   U.S.   Patent   0196859, filed November 7, 2011, and issued August 2, 2012.

 

Invited Reviews

Frey, K.M. (2015) Structure Enhanced Methods in the Development of Non-nucleoside Inhibitors Targeting HIV Reverse Transcriptase Variants. Future Microbiology. In Press.

Lectures and Presentations

Frey, K.M., Liu, J., Bolstad, D.E., Lombardo, M.N., Wright, D.L., Anderson, A.C. (2008) Crystallographic Complexes of Wild---type and Mutant MRSA DHFR Reveal Interactions for Lead Deign. North Eastern Structure Symposium: X---ray Crystallography and Computational Biology. Storrs, CT, USA.
Frey, K.M., Lombardo, M.N., Wright, D.L., Anderson, A.C. (2010) Towards the Understanding of Mutational Resistance Mechanisms in MRSA DHFR. Keystone Symposia: New Directions in Small Molecule Drug Discovery. Whistler, BC, Canada.
Frey, K.M., Georgiev, I., Donald, B.R., Anderson, A.C. (2010) Predicting Resistance Mutations Using Protein Design Algorithms. Institute for Drug Resistance: Shifting the Paradigms of Drug Resistance. Shrewsbury, MA, USA.
Frey, K.M., Gray, W.T., Spasov, K.A., Bollini, M., Cisneros, J.A., Gallardo-Masias, R., Jorgensen, W.L., Anderson, K.S. (2013) Structure-based Evaluation of Modified Derivatives in the Catechol Diether Series Targeting HIV-1 Reverse Transcriptase. Cambridge Health Institute: Structure-based Drug Design. Boston, MA, USA.
Frey, K.M. (2014) Computational and Structure-guided Design of Potent Inhibitors of HIV Reverse Transcriptase. Yale Pharmacology Retreat. Orange, CT, USA.

Grants/Contracts

2012-2015 - Structure Activity and Structure Property Relationships of Novel anti-HIV agents, Ruth L. Kirschstein National Research Service Award (NRSA) Postdoctoral Fellowship from the National Institute of Health, Institute of Allergy and Infectious Diseases (Award Number F32 AI104334)

Honors/Awards

2011 - Boehringer Ingelheim Predoctoral Fellowship Recipient

2011- Doctoral Dissertation Fellowship Recipient, University of Connecticut

2012 & 2013 – Editor Highlighted Publication, Journal of the American Chemical Society

Other Professional Activities

2012-2015 Associate Faculty Member, Biocatalysis Section, Faculty of 1000

2012-2015 Women in Science at Yale, Graduate Student Mentor

2013-2014 Yale Postdoctoral Advisory Committee

Professional Affiliations

American Association of Pharmaceutical Scientists

American Association of Colleges of Pharmacy

American Chemical Society

American Crystallographic Society

Institute for Drug Resistance