Curriculum Vitae

Name: Nathan E. Goldfarb, MS, PhD Address : 355 W 920 N A-308 Orem, UT 84057 Phone: (904) 716-7339 (cell) E-mail: natgoldfarb1@gmail.com LinkedIn: http://www.linkedin.com/in/nathangoldfarb Impact of Recent First Author Publications: In the area of tuberculosis (TB) drug discovery, Goldfarb, N.E. et al., PLOS Pathogens, 2014 unequivocally assign catalytic function to the TB drug target, Hip1, a serine hydrolase that had previously been erroneously reported to be devoid of proteolytic activity. We also validated that Hip1 indeed cleaves its proposed in vivo substrate, GroEL2. Based upon the Hip1 recognition site in GroEL2, we designed the first fluorescent substrate useful for screening compounds for novel inhibitors of Hip1. These results have profound implications on the preclinical drug discovery strategy utilized for this drug target; specifically, which class of inhibitors to screen for hit-to-lead optimization and which chemotypes to utilize as warheads on Hip1 targeting sequences for rational drug design. In the realm of HIV drug discovery, Goldfarb, N.E. et al., Biochemistry, 2015 provide the first experimental data illustrating a mechanism by which a distal mutation in HIV protease transmits its effect over a long distance, in order to result in weaker inhibitor binding in the active site of the protease. This mechanism describes a protease with an expanded active site and a conformational equilibrium shifted to the open, active form. Aside from providing illuminating insights on general protein dynamics, this provides proof-of-concept for the design of bulkier inhibitors that will take up the extra space in the active site and provides rational for the design of allosteric inhibitors that will shift the conformation of the protease back to the closed, inactive form.

Education

2009-2015 Postdoctoral Associate/Fellow, laboratory of Ben M. Dunn, PhD, Department of Biochemistry and Molecular Biology University of Florida, Gainesville, Florida

2003-2005 Postdoctoral Fellowship Schering-Plough Research Institute Kenilworth, New Jersey

1998-2003 PhD, Graduation date: August, 2003 Mentor, Ben M. Dunn, PhD Department of Biochemistry and Molecular Biology University of Florida, Gainesville, FL

1995-1998 Master of Science, Molecular Biology/Biotechnology Mentor: Cindy Putnam-Evans, PhD East Carolina University, Greenville, NC

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1990-1994 Bachelor of Arts and Sciences, Biology Department of Biology Virginia Polytechnic Institute and State University Blacksburg, VA

Industry Experience 2005-2007 Senior Scientist, Chemical Development Schering-Plough Research Institute Union, New Jersey 2007-2008 Chemist Vistakon Corporation (Johnson & Johnson) Jacksonville, FL

Teaching 2018-present Assistant Professor, Chemistry Utah Valley University Orem, UT CHEM 3600, Biological Chemistry CHEM 3605, Biochemistry Lab CHEM 1225, Chemistry II Lab CHEM 1120, Elementary Organic Biochemistry CHEM 482R CHEM 489R 2015-2017 Assistant Professor, Biochemistry Department of Pharmaceutics and Biomedical Sciences

California Health Sciences University Clovis, CA 93612 PHR 511 Biochemistry (Course Director and Instructor) (for P1 PharmD students; 30 TBL sessions) Team-based learning pedagogy

2012-2013 Mentor to Folasade Olajuyibe, PhD Visiting Professor, Nigeria Department of Biochemistry and Molecular Biology, University of Florida 2011-2012 Mentor to Wajahat Mahmood, doctoral student

Charles Darwin University/ Department of Biochemistry and Molecular Biology, University of Florida

2010-2011 Mentor to Sirilak Namwong, PhD Visiting Lecturer, Thailand

Department of Biochemistry and Molecular Biology, University of Florida

2008-2015 Mentor to undergraduate students: Sara Yu, Meray Ohanessian, Denis Chen, Jose Garcia, David Marcus, Ariana Cooke, Jeyko Garuz, Rachel Leeman, Stephanie Sanchez, Krina Patel, Edith Brach-Sanchez

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2008-2015 Mentor to lab techs: Jeyko Garuz, Daniil Shabashvilli, Tammy Flagg, Yang Tang

Service 2019 Chair, Faculty Search Committee, Utah Valley University 2018 National Science Foundation Scholarship Committee Member, Utah Valley

University 2016-present Faculty Advisor for Student National Pharmaceutical Association (SNPhA)

California Health Sciences University Chapter

2016-present Enterprise Risk Management Subcommittee California Health Sciences University

2015-present Faculty Council Committee, Research and Scholarship Committee,

Admissions and Progression Committee, Honor Council Committee, Departmental Chair Search Committee (Chairman)

2015-present Faculty Advisor for 8 graduate students

California Health Sciences University 2015-present Founded the California Health Sciences University Outdoor Adventure Club,

Faculty Advisor Volunteering

2017-present California State University, Fresno Department of Chemistry Dr. Cory Brooks’ Laboratory Tuberculosis Drug Discovery Research. Goldfarb, N.E., Principal Investigator. Mentor to one Master’s degree student: Ms. Shuchi Kakkad

Publications 1. Abell A., Perez BL., Njkin S., Parish T., Dunn BM., and Goldfarb NE. Discovery of a potent, reversible,

small molecule inhibitor of Hip1, a novel tuberculosis drug target. (manuscript in preparation).

2. Ostrov DA., Dunn BM., and Goldfarb NE. High resolution structure of tuberculosis drug target, Hip1, in its anhydroform. (manuscript in preparation).

3. Naffin-Olivos J., Daab, A., While A., Goldfarb NE, Rengarajan J. , Milne, A., Liu D., Baikovitz J., Dunn

B.M., Rengarajan J., Petsko G.A., and Ringe D. Crystal Structure of Hip1, a novel serine protease drug target for Tuberculosis. Biochemistry. 2017. 56 (19) 2435-2528. Front Cover of Journal.

4. Liu Z., Huang X., Hu L., Pham L., Poole KM., Tang Y., Mahon B., Tang W., Kunhua L., Goldfarb N.E.,

Dunn BM, McKenna R., Fanucci GE. Effects of Hinge Region Natural Polymorphisms on Human Immunodeficiency Virus-1 Protease Structure, Dynamics and Drug-Pressure Evolution. Journal of Biological Chemistry. 2016.

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5. Quiliano M., Mendoza A., Fong KY., Pabon A., Goldfarb NE., Fabing I., Vettorazii A., Lopez de Cerian A., Dunn BM., Garavito G., Wright DW., Deharo E., Perez-Silanes S., Aldana I., Galiano S. Exploring the scope of new arylamino alcohol derivatives: Synthesis, antimalarial evaluation, toxicological studies, and target exploration. Int J Parasito Drugs Drug Resist. 2016. 6. 184-198.

6. Mahindra A., Gangwal R., Bansal S, Goldfarb N.E., Dunn B.M., Sangamwar A.T., and Jain R. Antiplasmodial activity of short peptide-based compounds. RSC Advances. 2015. 5, 22674-22684.

7. Sing A.K., Rathore S., Tang Y., Goldfarb N., Dunn B.M., Rajendran V., Ghosh P.C., Singh N., Latha N.,

Singh B.K., Rawat M., and Rathi B. Hydroxyethylamine based pthalimides as a new class of plasmepsin inhibitors: design, synthesis, and antimalarial evaluation. PLOS ONE. 2015. 10. 1-20.

8. Goldfarb N.E., Georgieva M., Naffin-Olivos J., Madan-Lala R., Dong L., Bizzell E., Valinetz E., Brandt

G.S., Yu S., Shabashvili D.E., Ringe D., Dunn B.M., Petsko G.A, and Rengarajan J. Hip1, a novel serine protease drug target for Tuberculosis. PLOS Pathogens. 2014. 10(5):e1004132.

9. Goldfarb, N.E., Ohanessian, M., Garcia, P., Ostrov, D., and Dunn, B. Defective Hydrophobic Sliding

Mechanism and Active Site Expansion in HIV-1 Protease Drug Resistant Variant Gly48Thr/Leu89Met:Mechanisms for the Loss of Saquinavir Binding Potency. Biochemistry. 2015. 54:2, 422-33.

10. Jones S.A., Neilsen P.M., Siew L, Callen D.F., Goldfarb N.E., Dunn B.M., and Abell A.D. A Template-

Based Approach to Inhibitors of Calpain 2, 20S Proteasome, and HIV-1 Protease. ChemMedChem. 2013. doi: 10.1002/cmdc.201300387.

11. Goldfarb N.E. and Dunn B.M. Human immunodeficiency virus 2 retropepsin. Handbook of

Proteolytic Enzymes. 3 ed. vol 1. Rawlings, N.D., Salvesen, G. Elsevier Science Dewey. 2012. 199-203.

12. Goldfarb N.E. and Dunn B.M. Human immunodeficiency virus 1 retropepsin. Handbook of Proteolytic Enzymes. 3 ed. vol 1. Rawlings, N.D., Salvesen, G. Elsevier Science Dewey. 2012. 1. 190-198.

13. Li M., Gustchina A, Matúz K., Tözsér J., Namwong S., Dunn B., Goldfarb N.E., Wlodawer A. Structural

and biochemical characterization of the inhibitor complexes of XMRV protease. FEBS. 2011. 22:4413-24.

14. Goldfarb N.E., Lam M.T., Bose A.K., Patel A.P., and Dunn B.M. Electrostatic switches that mediate

the pH-dependent conformational change of “short” recombinant human pseudocathepsin D. Biochemistry. 2005. 44:48, 15725-33.

15. Beyer B.B., Goldfarb N.E., and Dunn B.M. Expression, purification, and characterization of aspartic

endopeptidases: Plasmodium plasmepsins and “short” recombinant human pseudocathepsin D. Current Protocols in Protein Science. 2003.

16. Wlowdawer A., Li M., Gustchina A., Zbigniew D., Uchida K., Oyama H., Oda K., Goldfarb N.E., and

Dunn B.M. Inhibitor complexes of the Pseudomonas serine-carboxyl proteinase. Biochemistry. 2001, 40:51, 15602-15611.

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17. Goldfarb N.E., Knoepfle N., and Putnam-Evans C. Construction of a psbC deletion strain in Synechocystis 6803. SAAS Bull. Biochem. Biotechnol. 1997, 10, 1-6.

Abstracts

1. Nathan Goldfarb, Sarah Yu, Daniil Shabashvilli, Maria Georgieva, Ranjna Madan-Lala, Jacqueline Naffin-Olivos, Gregory Petsko, Jyothi Rengarajan, and Ben M. Dunn. (2013) Hip1, a novel serine protease drug target for Tuberculosis. American Proteolysis Society. Kona, Hawaii.

2. Nathan Goldfarb, Sarah Yu, Daniil Shabashvilli, Maria Georgieva, Ranjna Madan-Lala, Jacqueline

Naffin-Olivos, Gregory Petsko, Jyothi Rengarajan, and Ben M. Dunn. (2013) Hip1, a novel serine protease drug target for Tuberculosis. Tuberculosis: Understanding the Enemy. (Keystone Symposium). pp. 135, Whistler, British Columbia, Canada.

3. Maria Georgieva, Jacqueline Naffin-Olivos, Ranjna Madan-Lala, Erica Bizzell, Nathan Goldfarb, Ben

Dunn, Gregory Petsko, and Jyothi Rengarajan. (2013) Complex interplay between Hip1 serine protease and its physiological substrate GroEL2: new insights into an M. tuberculosis immunomodulatory mechanism. Tuberculosis: Understanding the Enemy. (Keystone Symposium). Whistler, B.C., Canada.

4. Goldfarb, N.E., Yu, S., Shabashvilli, D., Georgieva, M., Madan-Lala, R., Naffin-Olivos, J., Petsko, G.,

Rengarajan, J., and Dunn, B. (2012) Biochemical Characterization Hip1, a Mycobacterium tuberculosis virulence factor. Emerging Pathogens Institute Research Day. pp. 38, Gaineseville, Florida.

5. Davila, A., Goldfarb, N.E., and Dunn B. (2012) Characterization of Plasmepsin 10 from Plasmodium

falciparum. Annual Biomedical Research Conference for Minority Students. San Jose, California.

6. Yu, S., Goldfarb, N.E., Shabashvilli, D., Georgieva, M., Madan-Lala, R., Naffin-Olivos, J., Petsko, G., Rengarajan, J., and Dunn, B. (2012) Expression, Refolding, and Purification of Hip1, a Mycobacterium tuberculosis drug target. Fourth Southeastern Mycobacteria Meeting, pp. 54. Atlanta, Georgia.

7. Goldfarb, N.E., Yu, S., Shabashvilli, D., Georgieva, M., Madan-Lala, R., Naffin-Olivos, J., Petsko, G., Rengarajan, J., and Dunn, B. (2012) Biochemical Characterization Hip1, a Mycobacterium tuberculosis virulence factor. Fourth Southeastern Mycobacteria Meeting. pp. 52, Atlanta, Georgia.

8. Goldfarb, N.E., Chen, Q., Robbins A., McKenna R., Dunn, B. (2012) 2.3 Å crystal structure of a drug

resistant HIV C N88D/L90M protease complexed with Saquinavir. Keystone Symposium, pp. 79. High-throughput Structural Biology. Keystone, Colorado.

9. Chen, D., Goldfarb N.E., Robbins A.H., McKenna R., and Dunn B. (2011) 2.3 Å crystal structure of a

drug resistant HIV C N88D/L90M protease complexed with saquinavir. Experimental BiologyMeeting (ASBMB), pp. 218. Washington, D.C.

10. Goldfarb, N.E., Shabashvilli, D., and Dunn, B. (2011) Expression and Refolding of Hip1, a

Mycobacterium tuberculosis virulence factor. The American Peptide Society, pp. 519. San Diego, California.

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11. Goldfarb, N.E., Bassily, O., Ghanem, A., Feiock, A., Dunn, B. (2009) Expression, purification, and refolding of HIV-protease containing drug resistant mutations. Keystone Symposia on Molecular Biology and Cellular Biology, pp. 85. Breckenridge, Colorado.

12. Goldfarb N.E., Mahmood W., and Dunn, B. (2011) Active site exploration and inhibitor discovery for a novel scabies aspartyl protease drug target. Experimental Biology Meeting (ASBMB), pp. 218. Washington, D.C.

13. Dunn B.M., Li M., Gustchina A., Oda K., Goldfarb N.E., Wlowdawer A. (2002) Inhibitor complexes of

the Pseudomonas serine-carboxyl proteinase. The Southeastern Branch of the American Society for Microbiology, pp. A19.

14. Goldfarb N.E., Lam M.T., Bose A.K., Patel A.P., and Dunn B.M. (2001) Evidence for E5, E180, and

D187 as ionic switches mediating pH-dependent autoregulation of “short” recombinant pseudocathepsin D. 2nd General Meeting of the International Proteolysis Society. Munich, Germany.

15. Beyer B., Chung A., Johnson J., Goldfarb N.E., Clemente J., Moose R., Perry K., and Dunn B.M. (2001)

Analysis of aspartic proteinase specificity utilizing targeted chromogenic combinatorial peptide libraries. FASEB Journal, vol. 15(5), pp. A539.

16. Lam M.T. and Goldfarb N.E. (2001) Inspection of putative ion switches in “short” recombinant

pseudocathepsin D. FASEB Journal, vol. 15(5), pp. A537.

17. Goldfarb N.E. and Dunn B.M. (2001) Determination of the role of E180Q in the pH-dependent conformational change of “short” recombinant pseudocathepsin D. FASEB Journal, vol. 15(5), pp. A1159.

18. Goldfarb N.E., Knoepfle N., and Putnam-Evans C. (1998) Mutagenesis of the CP43 protein of photosystem II in Synechocystis 6803. Journal of Elisha Mitchell Society.

19. Goldfarb N.E., Knoepfle N., and Putnam-Evans, C. (1998) The CP43 protein of photosystem II in Synechocystis 6803: Random mutagenesis of the large extrinsic loop. FASEB Journal, vol. 12(8), pp. A1443.

Invited Lectures

1. Drug Discovery for Infectious Diseases: The Long and Winding Road. Brigham Young University. Provo, Utah. 2018

2. Perspectives on Drug Design. Reedley College. Reedley, CA. 2016.

3. A Journey Through Drug Discovery. Sunnyside High school. UCSF Fresno Medical Program. Fresno, CA. 2016.

4. A Journey Through Drug Discovery. Reedley College. Reedley, CA. 2016.

5. Drug Discovery for Infectious Diseases. California State University, Fresno, CA. 2016.

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6. Drug Discovery for Infectious Diseases. Rosalind Franklin University, Chicago, IL. 2016

7. Drug Discovery for Infectious Diseases. California Health Sciences University. Clovis, CA, 2015.

8. Drug Discovery for Infectious Diseases. The New Jersey Institute of Technology. Newark, NJ. 2015.

9. Drug Discovery for Infectious Diseases. The University of the Pacific. Stockton, CA, 2015.

10. Enzyme Kinetics. The University of the Pacific. Stockton, CA, 2015.

11. Hip1, A Novel Serine Protease Drug Target. American Society for Biochemistry and Molecular Biology. Special Symposia Series: Membrane Anchored Serine Proteases. Potomac, MD, 2013.

12. Structure Based Drug Design for Infectious Diseases. Faculty Research Seminar Series. Dept. of Biochemistry and Molecular Biology. University of Florida, Gainesville, FL, 2012.

13. Inhibitor Discovery for Drug Targets. Science for Life Research Seminar. Howard Hughes Medical Institute. University of Florida, Gainesville, FL, 2012.

14. Presinilin 2 and hCat D: Two unique aspartyl proteinases. Honorary Postdoctoral Seminar. Schering-Plough Research Institute, NJ, 2005.

15. Inspection of putative ion switches in recombinant human “short” pseudocathepsin D. The 8th International Aspartic Protease Conference. Madeira, Portugal, 1999.

16. Random mutagenesis of 185T to 185I in the hydrophilic loop C of the CP43 protein of photosystem II. Annual Meeting North Carolina Academy of Sciences, Greensboro, NC, 1998.

Editorial Duties

2016-present Reviewer: Protein and Peptide Letters 2012 Referee: Uehara et al., Accelerated maturation of Tk-subtilisin by Leu-Pro

mutation at the C-terminus of propeptide due to non-optimal binding of propeptide to Tk-subtilisin. 2012 FEBS Journal.

Grants Submitted

2019 Collaborator on National Science Foundation Major Research Instrumentation Program: “Single crystal X-Ray diffractometer”. Dr. Stacey Smith, Principal Investigator, Brigham Young University, Provo, UT.

2018 Grants of Research for Engaged Educators and Novices (GREEN),

Utah Valley University. “Tuberculosis Drug Discovery: Optimization of Potent Hip1 Inhibitors by Structure-Based Drug Design”. Principal Investigator.

2010 “Structural and biochemical characterization of drug resistant HIV proteases

resulting from current front-line treatment protocols and the design of next

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generation protease inhibitors with improved efficacy”. amfAR The Foundation for AIDS Research.

2010 R21 “High Throughput Screening Assay for Screening of Potential Inhibitors for

HIV-1 protease”. 2011 “Prostate Cancer Drug Discovery: XMRV Protease Inhibitor Development.” Ruth

L. Kirschstein Research Service Award (NIH training grant). 2013 “Inhibitor discovery for Hip1, a novel Tuberculosis serine hydrolase drug target”.

Bill and Milenda Gates Foundation.

2014 R01 “Inhibitor discovery for Hip1, a novel Tuberculosis serine hydrolase drug target”.

Funding and Awards

2018 – 2019 $30,000 Grants of Research for Engaged Educators and Novices (GREEN), Utah Valley University. “Tuberculosis Drug Discovery: Optimization of Potent Hip1 Inhibitors by Structure-Based Drug Design”. Principal Investigator.

2011 - 2012 $110,000 Ruth L. Kirschstein Research Service Award (NIH training grant)

Prostate Cancer Drug Discovery: XMRV Protease Inhibitor Development.

2001, 2003 Travel Grant Recipient

University of Florida

2001 Travel Grant Recipient International Proteolysis Society

1996 McDaniel Scholarship East Carolina University

Affiliations

2016-present American Peptide Society 2016-present International Proteolysis Society 2010, 2014, 2016 American Chemical Society 2011 Protein Society 2010 American Society for Biochemistry and Molecular Biology 1998-2003 Sigma Xi, The Scientific Research Society 1994 Phi Sigma, Biology/Biochemistry Honors Society 1991-1994 Sigma Pi Fraternity International

BRIEF DESCRIPTION OF JOB DUTIES-

A. Assistant Professor-Department of Chemisty, Utah Valley University I am an Assistant Professor specializing in drug discovery for infectious diseases. I have three major responsibilities: research and scholarship, service, and teaching. I operate a laboratory with

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cutting edge equipment and mentor six undergraduates in the lab. Additionally, I teach a variety of upper and lower level chemistry courses and serve on a number of university committees.

B. Education My teaching activities include teaching students Biochemistry. I utilize the Team-Based Learning pedagogy which utilizes Bloom’s Taxonomy to structure curriculum learning objectives, assessments, and activities. The course prepares the student for understanding: 1) molecular mechanisms of medications and their effects on the cells of the body; 2) molecular mechanisms of disease and points of intervention in the disease process by medications; 3) drug discovery from bench to bedside, and 4) molecular concepts underlying pharmacogenomics and how pharmacogenomics can impact medication therapy of patients. This understanding will prepare the student for the pharmacology and patient care series of courses by laying the foundation for understanding disease processes and the mechanisms by which various classes of medications exert their action. This understanding also prepares the student for communicating with other health care professionals during the treatment of their patients. I also lecture outside of the university on the modern paradigm of drug discovery, as well as drug discovery for TB, malaria, and HIV. Sharing my passion for science and education with the community is a commitment of mine. I hope to engage young minds such that they have confidence to pursue their educational goals.

C. Research and Development My basic and translational research includes understanding protein structure and function, to the end of discovering novel therapeutics for tuberculosis (TB), HIV, and malaria. Since drug resistance is a major problem with these global epidemics, new drugs are urgently needed.

1) Tuberculosis Drug Discovery My primary research focuses on the tuberculosis drug target, Hip1 (hydrolase important for pathogenesis), a cell envelope-associated hydrolase. Hip1 is a virulence factor that plays pivotal roles in both pathogenic strategies of cell envelope maintenance and dampening of the host cell proinflammatory responses. We have determined that Hip1 is a novel serine protease and have discovered novel chromogenic and fluorescent substrates for the enzyme. Additionally, we have validated that GroEL2 is a biological substrate for Hip1. This work was published PLOS Pathogens (2014). Recently, we have determined the 2.6 Ǻ resolution structure of the apo form of Hip1 in collaboration with Greg Petsko’s group at Brandeis University. This was reported in the journal, Biochemistry (May 2017), and made the front cover of the journal. Furthermore, we are about to publish a higher, 2.1 Ǻ resolution structure of the anhydro-form of Hip1 (Goldfarb, et al., manuscript in preparation) that unequivocally assigns function to the catalytic serine residue of the catalytic triad. We have initiated a drug discovery campaign that includes hit identification through the use of mixture based libraries, as well as the de novo synthesis of inhibitors composed of Hip1 targeting sequences containing various types of warheads that inactivate serine proteases. To date, we have discovered several novel, potent, reversible inhibitors of Hip1 that are potent in the picomolar to nanomolar range. We are currently collecting X-ray diffraction data on crystals of the complexes of the enzyme and inhibitors (Goldfarb, et al., manuscript in preparation). We are also having the compounds tested for efficacy against M. tuberculosis in collaboration with Dr. Tanya Parrish at the University of Washington. Additionally, in collaboration with the Torrey

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Pines Institute for Molecular Studies (Jupiter, FL), we have discovered two lead molecular scaffolds showing excellent inhibition of Hip1. We perform hit-to-lead optimization using both structure and computer aided drug design, in hand with structure-activity relationship studies. We test lead compounds for efficacy and toxicity in cell based models, as well as in a murine model for TB. Our goal is to discover both small molecule and peptidomimetic serine protease inhibitors with excellent ADMET and efficacy profiles. Additionally, our efforts to develop an array of potent and selective inhibitors will provide a new toolbox of chemical probes useful for the dissection of proteolytic pathways involving serine proteases. These probes may unveil additional serine protease drug targets for TB. Long-range aspirations of mine are to investigate a number of other serine proteases that have been identified as virulence factors for M. tuberculosis (Mtb) with the ultimate goal of applying our drug discovery technologies to these targets to develop new Mtb antibiotics.

2) HIV Drug Discovery Regarding HIV drug discovery, I am interested in understanding how mutations in HIV protease (PR), an aspartyl protease, result in decreased susceptibility to current FDA approved protease inhibitors (PI) that are designed to bind in the active site of the closed conformation of the enzyme. The effects of mutations in amino acid residues that compose the active site are more easily understood, since they directly interact with the inhibitor; however, mechanisms by which mutations distal to the active site transmit their deleterious effect on drug binding have perplexed researchers. In 2015, we were able to solve a crystal structure of HIV protease containing the drug resistant mutations Gly48Thr/Leu89Met bound with the active site inhibitor, saquinavir, and this was published in the journal, Biochemistry. An extremely detailed analysis of the structure in comparison to the native structure bound with saquinavir, in addition to sophisticated molecular dynamics simulations facilitated the discovery of a novel mechanism by which a distal mutation weakens inhibitor binding. This is a result of modified van der Waals interactions in the hydrophobic core of PR that affect the conformational dynamics of PR resulting in a PR with a more open conformation and enlarged active site. As a result, our findings support taking an alternative approach to mitigating drug resistance by developing bulkier inhibitors that occupy the enlarged active site of PR or by screening for allosteric inhibitors that bind and force the open conformation of PR to the closed conformation.

3) Malaria Drug Discovery

Although great strides have been made to reduce the global mortality rate from malaria, drug resistance still remains a problem with current malaria drugs regimens. Additionally, a new malaria drug has not been developed in over fifty years, while the World Health Organization estimates nearly 500,000 deaths from malaria in 2015. Consequently, new antimalarial drugs are needed. As a result of the genome sequencing of P. falciparum, the parasite that causes malaria, ten aspartyl protease genes were identified; however, based on knock-out studies and the temporal and spatial expression of the gene products, only three aspartyl proteases, Plasmepsin V, IX and X, have been identified as valid drug targets for the development of novel malaria therapeutics. We are currently engaged in optimizing the expression and refolding of these challenging proteins. Although many of the other unnecessary Plasmepsins (Plasmepsins I, II, IV, and VI) behave well in terms of expression and refolding, Plasmepsins IV and X are longer and contain inserted amino acid sequences that add complexity to the refolding problem. We are utilizing protein engineering techniques, in addition to a variety of different expression

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systems, in order to produce milligram quantities of correctly folded material useful for structure-based drug design. Our long-term goal is to move these targets into our pipeline for hit-to-lead generation.

AREAS OF SPECIALIZATION- Enzyme Kinetics and Structure-based drug design My participation in the field of biochemistry and structural biology since 1995 has allowed me

to develop a toolbox enabling me to study protein structure and function to the end of developing novel drug target modulators.

A. As a graduate student at East Carolina University:

1. Molecular cloning, mutagenesis, DNA sequencing 2. Random mutagenesis, gene deletion using homologous recombination

B. As a graduate student at the University of Florida: 1. Large scale protein production and purification 2. Site-directed mutagenesis 3. Protein refolding 4. Enzyme kinetics (Km, Ki, kcat/Km) 5. Kinetic and molecular modeling

C. As a postdoctoral fellow at the Schering-Plough Research Institute

1. Insect cell culture 2. Reconstitution of membrane protein complex containing gamma secretase for

Alzheimer’s Disease research

D. As a Senior Scientist at Schering-Plough Research Institute 1. Project leadership and management skills 2. Biotransformation for chiral separations 3. GLP

E. As a Postdoctoral Fellow at the University of Florida

1. RO1, R21, T32 submitted 2. High throughput assay development for hit-to-lead generation 3. Protein crystallization 4. Analysis of crystal structures utilizing Pymol, PROCHECK, CCP4, COOT 5. Introduction to molecular dynamic simulations

F. As an Assistant Professor at California Health Sciences University

1. Molecular Docking using UCSF Chimera and Autodock Vina

G. As an Assistant Professor at California Health Sciences University

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TEACHING, ADVISING AND/OR INSTRUCTIONAL ACCOMPLISHMENTS 2019 CHEM 489R Internship Program 2019 CHEM 482R Independent Research for Undergraduates 2019 CHEM 1120 Elementary Organic Biochemistry 2018-present CHEM 3600 Biological Chemistry 2018-present CHEM 3605 Biological Chemistry Lab 2015, 2016 PHR 511 Biochemistry (Course Director and Instructor); Team-based learning

pedagogy 30 sessions; 30 basic application tests; 30 Individual readiness tests; 2 exams At the University of Florida, I mentored over 20 undergraduate, graduate, and postdoctoral researchers in Ben Dunn’s lab. Several students were extremely productive, and their hard work resulted in publications in top tier journals. At the California Health Sciences University, I served as the faculty advisor for 8 PharmD graduate students. At the California Health Sciences University, I served as the faculty advisor for Student National Pharmaceutical Association. At Utah Valley University, I currently mentor six undergraduate students in my laboratory. Their projects involve various aspects of drug discovery for Tuberculosis.

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