Our laboratory is interested in the development and application of strategies and technologies that enable the high-throughput/large-scale exploration of biological function. These efforts typically take advantage of automation and robotics to achieve the efficiencies and speed required to realize the desired rates of data generation and discovery. This cutting-edge infrastructure has been applied to a number of important biomedical areas to achieve new understanding and new therapeutic opportunities.

Our work on the large-scale annotation of enzyme function is helping to define the metabolic repertoire that exists in Nature and is providing new insights into the contributions of the gut microbiome to human health, the realization of new chemical processes for industry, and expanding our understanding of critical environmental issues, including global nutrient cycles and the evolution of complex microbial communities. Our high-resolution structural and functional analysis of the mammalian immune system has resulted in unprecedented understanding of the molecular mechanisms that control immunity and are guiding the development of novel strategies and reagents (e.g., biologics) for the treatment of infectious diseases, autoimmune diseases and cancers.

Quayle SN, Girgis N, Thapa DR, Merazga Z, Kemp MM, Histed A, Zhao F, Moreta M, Ruthardt P, Hulot S, Nelson A, Kraemer LD, Beal DR, Witt L, Ryabin J, Soriano J, Haydock M, Spaulding E, Ross JF, Kiener PA, Almo S, Chaparro R, Seidel R, Suri A, Cemerski S, Pienta KJ, Simcox ME. (2020) "CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies." Clin Cancer Res. 26(8), 1953-1964. PMID:31964784.

Funabashi M, Grove TL, Wang M, Varma Y, McFadden ME, Brown LC, Guo C, Higginbottom S, Almo SC, Fischbach MA. (2020) "A metabolic pathway for bile acid dehydroxylation by the gut microbiome." Nature 582(7813), 566-570. PMC7319900.

Liu W, Garrett SC, Fedorov EV, Ramagopal UA, Garforth SJ, Bonanno JB, Almo SC. (2019) "Structural Basis of CD160:HVEM Recognition." Structure 27(8), 1286-1295.e4. PMC7477951.

Gizzi AS, Grove TL, Arnold JJ, Jose J, Jangra RK, Garforth SJ, Du Q, Cahill SM, Dulyaninova NG, Love JD, Chandran K, Bresnick AR, Cameron CE, Almo SC.  (2018) “A naturally occurring antiviral ribonucleotide encoded by the human genome.” Nature 558, 610-614.  PMC6026066.

Ghosh A, Ramagopal UA, Bonanno JB, Brenowitz M, Almo SC. (2018) “Structures of the L27 Domain of Disc Large Homologue 1 Protein Illustrate a Self-Assembly Module.” Biochemistry 57, 1293-1305. PMC6568269.

Ramagopal UA, Liu W, Garrett-Thomson SC, Bonanno JB, Yan Q, Srinivasan M, Wong SC, Bell A, Mankikar S, Rangan VS, Deshpande S, Korman AJ, Almo SC. (2017) “Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab.”  Proc Natl Acad Sci U S A. 114, E4223-E4232.  PMC5448203.

Lázár-Molnár E, Scandiuzzi L, Basu I, Quinn T, Sylvestre E, Palmieri E, Ramagopal UA, Nathenson SG, Guha C, Almo SC. (2017) “Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy.”  EBioMedicine. 17, 30-44. PMC5360572. 

Samanta D, Guo H, Rubinstein R, Ramagopal UA, Almo SC. (2017) “Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2.” Mol Immunol. 81, 51-159. PMC5220579.

Liu W, Ramagopal U, Cheng H, Bonanno JB, Toro R, Bhosle R, Zhan C, Almo SC. (2016) “Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.” Structure 24, 2016-2023. PMID:27806260.

Yadava U, Vetting MW, Al Obaidi N, Carter MS, Gerlt JA, Almo SC. (2016) “Structure of an ABC transporter solute-binding protein specific for the amino sugars glucosamine and galactosamine.” Acta Crystallogr F Struct Biol Commun. 72, 467-472. PMC4909247.

Liu W, Vigdorovich V, Zhan C, Patskovsky Y, Bonanno JB, Nathenson SG, Almo SC. (2015) “Increased Heterologous Protein Expression in Drosophila S2 Cells for Massive Production of Immune Ligands/Receptors and Structural Analysis of Human HVEM.” Mol Biotechnol. 57, 914-922. PMID:26202493.

Kim J, Xiao H, Koh J, Wang Y, Bonanno JB, Thomas K, Babbitt PC, Brown S, Lee YS, Almo SC. (2015) “Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification.” Nucleic Acids Res. 43, 4602-4613.  PMC4482062.

 Vetting MW, Al-Obaidi N, Zhao S, San Francisco B, Kim J, Wichelecki DJ, Bouvier JT, Solbiati JO, Vu H, Zhang X, Rodionov DA, Love JD, Hillerich BS, Seidel RD, Quinn RJ, Osterman AL, Cronan JE, Jacobson MP, Gerlt JA, Almo SC. (2015) “Experimental strategies for functional annotation and metabolism discovery: targeted screening of solute binding proteins and unbiased panning of metabolomes.” Biochemistry 54, 909-931. PMC4310620.

Samanta D, Almo SC. (2015) “Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity.” Cell Mol Life Sci. 72, 645-658. PMID: 25326769.

Liu W, Zhan C, Cheng H, Kumar PR, Bonanno JB, Nathenson SG, Almo SC. (2014) “Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly.” Structure 22, 1252-1262.  PMC4163024.

Bandaranayake AD, Almo SC. (2014) “Recent advances in mammalian protein production.” FEBS Lett. 588, 253-260. PMC3924552.

Kim J, Xiao H, Bonanno JB, Kalyanaraman C, Brown S, Tang X, Al-Obaidi NF, Patskovsky Y, Babbitt PC, Jacobson MP, Lee YS, Almo SC. (2013) “Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function.” Nature 498, 123-126.  PMC3895326.

Kim J, Almo SC. (2013) “Structural basis for hypermodification of the wobble uridine in tRNA by bifunctional enzyme MnmC.” BMC Struct Biol. 13:5. PMC3648344.

Vigdorovich V, Ramagopal UA, Lázár-Molnár E, Sylvestre E, Lee JS, Hofmeyer KA, Zang X, Nathenson SG, Almo SC. (2013) “Structure and T cell inhibition properties of B7 family member, B7-H3.” Structure 21, 707-717. PMC3998375.

Soniat M, Sampathkumar P, Collett G, Gizzi AS, Banu RN, Bhosle RC, Chamala S, Chowdhury S, Fiser A, Glenn AS, Hammonds J, Hillerich B, Khafizov K, Love JD, Matikainen B, Seidel RD, Toro R, Rajesh Kumar P, Bonanno JB, Chook YM, Almo SC. (2013) “Crystal structure of human Karyopherin β2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2.” J Struct Funct Genomics 14, 31-35. PMC3681870.

Sampathkumar P, Kim SJ, Upla P, Rice WJ, Phillips J, Timney BL, Pieper U, Bonanno JB, Fernandez-Martinez J, Hakhverdyan Z, Ketaren NE, Matsui T, Weiss TM, Stokes DL, Sauder JM, Burley SK, Sali A, Rout MP, Almo SC. (2013) “Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex.” Structure 21, 560-571. PMC3755625.