Jimmy D. Gollihar

Jimmy D. Gollihar, PhD

Professor of Pathology and Genomic Medicine, Academic Institute
Jerold B. Katz Investigator, Academic Institute
Full Member, Research Institute
Houston Methodist


Gollihar Lab - ADAPT


Description of Research

I am a Scientist and the Head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute (HMRI). My work encompasses a broad range of engineering biology, from the design of simple genetic “parts” and circuits to protein engineering and industrial biomanufacturing. I use synthetic biology applications to domesticate non-model organisms and engineer proteins or biosynthetic pathways with therapeutic and industrial potential. I apply a holistic approach to protein engineering by integrating concepts from directed evolution, rational design, and artificial intelligence to create biological countermeasures, diagnostics, and vaccine candidates. Recently, my group has contributed to the genomic surveillance and characterization of SARS-CoV-2, B-cell repertoire mining for neutralization and protection assays, and the engineering of enzymes intended for mRNA vaccine manufacturing.

Early in the pandemic, we recognized that the absence of a SARS-CoV-2 antigen created an international bottleneck for the development of COVID-19 diagnostics and therapeutics. To address this constraint, we created several stable cell lines for mass production of spike antigen in collaboration with Dr. Jason McLellan. Through collaborations at the University of Texas at Austin and Texas A&M University, we developed a high-throughput pipeline to produce spike and receptor-binding domain (RBD) antigen for serological testing. We produced and distributed spike and RBD antigen nationwide to other academic, governmental, and commercial partners. Notably, our antigen was used to screen convalescent plasma at the HMRI to enable timely treatment of critically ill patients. The antigen was also used in numerous antibody and small-molecule discovery efforts across the nation and Europe. These efforts formed the basis of numerous production runs across industry and academic labs throughout the US.

We also invented methods to characterize spike mutations emerging in variants of concern (VOCs) using mammalian synthetic biology. The SARS-CoV-2 spike protein is a critical component of subunit vaccines and a target for neutralizing antibodies. Further, spike undergoes immunogenic selection resulting in variants that increase infectivity and partially escape neutralization by convalescent plasma. We developed Spike Display, a high-throughput, automated platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed variant SARS-CoV-2 spikes for gene expression, ACE2 binding, and recognition of known neutralizing antibodies (nAbs). Our method has been used to screen VOCs in near real-time and afforded the opportunity to understand mechanisms of escape and virus evolution. We anticipate that Spike Display will accelerate antigen design, structure-function studies, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.

The ongoing adaptive evolution of SARS-CoV-2 genome sequences to create more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing vaccines and therapeutic antibodies. Increased genomic surveillance and methods to rapidly develop and assess effective interventions are critical for interrogating adaptive immunity and developing rapid-response biological countermeasures to emerging pathogens. Using our foundry, we discovered SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform that we developed during the COVID-19 pandemic. We identified antibodies from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Our strategies should prove broadly applicable to adaptive immunity interrogations of emerging pathogenic threats.

In addition to our pandemic response work, I have spent the last four years as a DoD scientist. In that time, I designed and built the Army’s Biological Foundry co-located at the University of Texas at Austin. This work increased DoD capability in the field of synthetic biology for early-stage research efforts. From 2019 to 2021, I also served as the government CTO of the Bioindustrial Manufacturing Innovation Institute–BioMADE. As the technical architect of the institute, I led the creation of a public-private partnership to develop innovations at scale for biological production of non-medical products. Prior to that, I led an in-house R&D effort in the private sector.

Publications

Engineering a human P2X2 receptor with altered ligand selectivity in yeast
Gardner, EC, Tramont, C, Bachanová, P, Wang, C, Do, H, Boutz, DR, Kar, S, Zemelman, BV, Gollihar, JD & Ellington, AD 2024, , Journal of Biological Chemistry, vol. 300, no. 5, 107248. https://doi.org/10.1016/j.jbc.2024.107248

SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode
Goike, J, Hsieh, CL, Horton, AP, Gardner, EC, Zhou, L, Bartzoka, F, Wang, N, Javanmardi, K, Hebert, A, Abbasi, SA, Xie, X, Xia, H, Shi, PY, Renberg, R, Segall-Shapiro, T, Terrace, CI, Wu, W, Shroff, R, Byrom, M, Ellington, AD, Marcotte, EM, Musser, JM, Kuchipudi, SV, Kapur, V, Georgiou, G, Weaver, S, Dye, JM, Boutz, DR, McLellan, JS & Gollihar, JD 2023, , Communications Biology, vol. 6, 1250, pp. 1250. https://doi.org/10.1038/s42003-023-05649-6

The response of mpox-associated inflammatory syndrome to steroid therapy
Arias, CA, Miller, WR, Olsen, RJ, Gollihar, J & Armstrong, A 2023, , The Lancet Infectious Diseases, vol. 23, no. 8, pp. e323-e324. https://doi.org/10.1016/S1473-3099(22)00876-3

Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols
Bean, BDM, Mulvihill, CJ, Garge, RK, Boutz, DR, Rousseau, O, Floyd, BM, Cheney, W, Gardner, EC, Ellington, AD, Marcotte, EM, Gollihar, JD, Whiteway, M & Martin, VJJ 2022, , Nature Communications, vol. 13, no. 1, 2882. https://doi.org/10.1038/s41467-022-30570-7

Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols
Bean, BDM, Mulvihill, CJ, Garge, RK, Boutz, DR, Rousseau, O, Floyd, BM, Cheney, W, Gardner, EC, Ellington, AD, Marcotte, EM, Gollihar, JD, Whiteway, M & Martin, VJJ 2022, , Nature Communications, vol. 13, no. 1, 2882, pp. 2882. https://doi.org/10.1038/s41467-022-30570-7, https://doi.org/10.1038/s41467-022-30570-7

Signals of Significantly Increased Vaccine Breakthrough, Decreased Hospitalization Rates, and Less Severe Disease in Patients with Coronavirus Disease 2019 Caused by the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 in Houston, Texas
Christensen, PA, Olsen, RJ, Long, SW, Snehal, R, Davis, JJ, Ojeda Saavedra, M, Reppond, K, Shyer, MN, Cambric, J, Gadd, R, Thakur, RM, Batajoo, A, Mangham, R, Pena, S, Trinh, T, Kinskey, JC, Williams, G, Olson, R, Gollihar, J & Musser, JM 2022, , American Journal of Pathology, vol. 192, no. 4, pp. 642-652. https://doi.org/10.1016/j.ajpath.2022.01.007

Orthogonal control of gene expression in plants using synthetic promoters and CRISPR-based transcription factors
Kar, S, Bordiya, Y, Rodriguez, N, Kim, J, Gardner, EC, Gollihar, JD, Sung, S & Ellington, AD 2022, , Plant Methods, vol. 18, no. 1, 42, pp. 42. https://doi.org/10.1186/s13007-022-00867-1

Delta Variants of SARS-CoV-2 Cause Significantly Increased Vaccine Breakthrough COVID-19 Cases in Houston, Texas
Christensen, PA, Olsen, RJ, Long, SW, Subedi, S, Davis, JJ, Hodjat, P, Walley, DR, Kinskey, JC, Ojeda Saavedra, M, Pruitt, L, Reppond, K, Shyer, MN, Cambric, J, Gadd, R, Thakur, RM, Batajoo, A, Mangham, R, Pena, S, Trinh, T, Yerramilli, P, Nguyen, M, Olson, R, Snehal, R, Gollihar, J & Musser, JM 2022, , American Journal of Pathology, vol. 192, no. 2, pp. 320-331. https://doi.org/10.1016/j.ajpath.2021.10.019

Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein
Javanmardi, K, Segall-Shapiro, TH, Chou, CW, Boutz, DR, Olsen, RJ, Xie, X, Xia, H, Shi, PY, Johnson, CD, Annapareddy, A, Weaver, S, Musser, JM, Ellington, AD, Finkelstein, IJ & Gollihar, JD 2022, , Cell Host and Microbe, vol. 30, no. 9, pp. 1242-1254.e6. https://doi.org/10.1016/j.chom.2022.07.016

Rapid characterization of spike variants via mammalian cell surface display
Javanmardi, K, Chou, CW, Terrace, CI, Annapareddy, A, Kaoud, TS, Guo, Q, Lutgens, J, Zorkic, H, Horton, AP, Gardner, EC, Nguyen, G, Boutz, DR, Goike, J, Voss, WN, Kuo, HC, Dalby, KN, Gollihar, JD & Finkelstein, IJ 2021, , Molecular Cell, vol. 81, no. 24, pp. 5099-5111.e8. https://doi.org/10.1016/j.molcel.2021.11.024

Trajectory of Growth of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in Houston, Texas, January through May 2021, Based on 12,476 Genome Sequences
Olsen, RJ, Christensen, PA, Long, SW, Subedi, S, Hodjat, P, Olson, R, Nguyen, M, Davis, JJ, Yerramilli, P, Saavedra, MO, Pruitt, L, Reppond, K, Shyer, MN, Cambric, J, Gadd, R, Thakur, RM, Batajoo, A, Finkelstein, IJ, Gollihar, J & Musser, JM 2021, , American Journal of Pathology, vol. 191, no. 10, pp. 1754-1773. https://doi.org/10.1016/j.ajpath.2021.07.002

Discovery of new vascular disrupting agents based on evolutionarily conserved drug action, pesticide resistance mutations, and humanized yeast
Garge, RK, Cha, HJ, Lee, C, Gollihar, JD, Kachroo, AH, Wallingford, JB & Marcotte, EM 2021, , Genetics, vol. 219, no. 1, iyab101. https://doi.org/10.1093/genetics/iyab101

Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes
Voss, WN, Hou, YJ, Johnson, NV, Delidakis, G, Kim, JE, Javanmardi, K, Horton, AP, Bartzoka, F, Paresi, CJ, Tanno, Y, Chou, CW, Abbasi, SA, Pickens, W, George, K, Boutz, DR, Towers, DM, McDaniel, JR, Billick, D, Goike, J, Rowe, L, Batra, D, Pohl, J, Lee, J, Gangappa, S, Sambhara, S, Gadush, M, Wang, N, Person, MD, Iverson, BL, Gollihar, JD, Dye, JM, Herbert, AS, Finkelstein, IJ, Baric, RS, McLellan, JS, Georgiou, G, Lavinder, JJ & Ippolito, GC 2021, , Science, vol. 372, no. 6546, pp. 1108-1112. https://doi.org/10.1126/science.abg5268

Limited window for donation of convalescent plasma with high live-virus neutralizing antibody titers for COVID-19 immunotherapy
Gontu, A, Srinivasan, S, Salazar, E, Nair, MS, Nissly, RH, Greenawalt, D, Bird, IM, Herzog, CM, Ferrari, MJ, Poojary, I, Katani, R, Lindner, SE, Minns, AM, Rossi, R, Christensen, PA, Castillo, B, Chen, J, Eagar, TN, Yi, X, Zhao, P, Leveque, C, Olsen, RJ, Bernard, DW, Gollihar, J, Kuchipudi, SV, Musser, JM & Kapur, V 2021, , Communications Biology, vol. 4, no. 1, 267. https://doi.org/10.1038/s42003-021-01813-y

Sequence Analysis of 20,453 Severe Acute Respiratory Syndrome Coronavirus 2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern
Long, SW, Olsen, RJ, Christensen, PA, Subedi, S, Olson, R, Davis, JJ, Saavedra, MO, Yerramilli, P, Pruitt, L, Reppond, K, Shyer, MN, Cambric, J, Finkelstein, IJ, Gollihar, J & Musser, JM 2021, , American Journal of Pathology, vol. 191, no. 6, pp. 983-992. https://doi.org/10.1016/j.ajpath.2021.03.004

Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization
Salazar, E, Kuchipudi, SV, Christensen, PA, Eagar, T, Yi, X, Zhao, P, Jin, Z, Long, SW, Olsen, RJ, Chen, J, Castillo, B, Leveque, C, Towers, D, Lavinder, J, Gollihar, J, Cardona, J, Ippolito, G, Nissly, R, Bird, I, Greenawalt, D, Rossi, RM, Gontu, A, Srinivasan, S, Poojary, I, Cattadori, IM, Hudson, PJ, Josleyn, NM, Prugar, L, Huie, K, Herbert, A, Bernard, DW, Dye, JM, Kapur, V & Musser, JM 2020, , Journal of Clinical Investigation, vol. 130, no. 12, pp. 6728-6738. https://doi.org/10.1172/JCI141206

Discovery of novel gain-of-function mutations guided by structure-based deep learning
Shroff, R, Cole, AW, Diaz, DJ, Morrow, BR, Donnell, I, Annapareddy, A, Gollihar, J, Ellington, AD & Thyer, R 2020, , ACS Synthetic Biology, vol. 9, no. 11, pp. 2927-2935. https://doi.org/10.1021/acssynbio.0c00345

Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG
Salazar, E, Christensen, PA, Graviss, EA, Nguyen, DT, Castillo, B, Chen, J, Lopez, BV, Eagar, TN, Yi, X, Zhao, P, Rogers, J, Shehabeldin, A, Joseph, D, Masud, F, Leveque, C, Olsen, RJ, Bernard, DW, Gollihar, J & Musser, JM 2021, , American Journal of Pathology, vol. 191, no. 1, pp. 90-107. https://doi.org/10.1016/j.ajpath.2020.10.008, https://doi.org/10.1016/j.ajpath.2020.10.008

Treatment of Coronavirus Disease 2019 Patients with Convalescent Plasma Reveals a Signal of Significantly Decreased Mortality
Salazar, E, Christensen, PA, Graviss, EA, Nguyen, DT, Castillo, B, Chen, J, Lopez, BV, Eagar, TN, Yi, X, Zhao, P, Rogers, J, Shehabeldin, A, Joseph, D, Leveque, C, Olsen, RJ, Bernard, DW, Gollihar, J & Musser, JM 2020, , American Journal of Pathology, vol. 190, no. 11, pp. 2290-2303. https://doi.org/10.1016/j.ajpath.2020.08.001

Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area
Long, SW, Olsen, RJ, Christensen, PA, Bernard, DW, Davis, JJ, Shukla, M, Nguyen, M, Saavedra, MO, Yerramilli, P, Pruitt, L, Subedi, S, Kuo, HC, Hendrickson, H, Eskandari, G, Nguyen, HAT, Long, JH, Kumaraswami, M, Goike, J, Boutz, D, Gollihar, J, McLellan, JS, Chou, CW, Javanmardi, K, Finkelstein, IJ & Musser, JM 2020, , mBio, vol. 11, no. 6, e02707-20, pp. 1-30. https://doi.org/10.1128/mBio.02707-20