<p style="text-align: justify;">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.</p>
<p style="text-align: justify;">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.</p>

<p>Dr. Steven Almo is an internationally recognized leader in the field of structural biology. His lab uses high-resolution X-ray crystallography to determine the shapes and structures of proteins to better understand their function and help develop new drugs. The goal is to make immunotherapy treatments that more precisely and effectively treat a variety of cancers while causing far fewer side effects than current therapies.&nbsp;</p>
<p>Dr. Almo&rsquo;s large-scale work on enzyme function has provided insights on both the gut microbiome&rsquo;s contributions to human health and new chemical processes for industry. His research also has expanded the understanding of critical environmental issues, including global nutrient cycles and the evolution of complex microbial communities.</p>
<p>He is a member of the American Society for Cell Biology and the American Crystallographic Association. He has served on NIH study sections and review panels, on the American Cancer Society&rsquo;s Peer Review Committee on Cancer Drug Development, and on the editorial board of the <em>International Archives of Allergy and Immunology</em>.&nbsp;</p>

<p style="text-align: justify;">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." <em>Clin Cancer Res.</em> <strong>26(8)</strong>, 1953-1964. PMID:31964784.</p>
<p style="text-align: justify;">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." <em>Nature</em>&nbsp;<strong>582(7813)</strong>, 566-570. PMC7319900.</p>
<p style="text-align: justify;">Liu W, Garrett SC, Fedorov EV, Ramagopal UA, Garforth SJ, Bonanno JB, Almo SC. (2019) "Structural Basis of CD160:HVEM Recognition." <em>Structure</em> <strong>27(8)</strong>, 1286-1295.e4. PMC7477951.</p>
<p style="text-align: justify;">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. &nbsp;(2018) &ldquo;A naturally occurring antiviral ribonucleotide encoded by the human genome.&rdquo; <em>Nature </em><strong>558</strong>, 610-614.&nbsp; PMC6026066.</p>
<p style="text-align: justify;">Ghosh A, Ramagopal UA, Bonanno JB, Brenowitz M, Almo SC. (2018) &ldquo;Structures of the L27 Domain of Disc Large Homologue 1 Protein Illustrate a Self-Assembly Module.&rdquo; <em>Biochemistry</em> <strong>57, </strong>1293-1305. PMC6568269.</p>
<p style="text-align: justify;">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) &ldquo;Structural basis for cancer immunotherapy by the first-in-class checkpoint inhibitor ipilimumab.&rdquo; &nbsp;<em>Proc Natl Acad Sci U S A</em>. <strong>114</strong>, E4223-E4232. &nbsp;PMC5448203.</p>
<p style="text-align: justify;">L&aacute;z&aacute;r-Moln&aacute;r E, Scandiuzzi L, Basu I, Quinn T, Sylvestre E, Palmieri E, Ramagopal UA, Nathenson SG, Guha C, Almo SC. (2017) &ldquo;Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy.&rdquo; &nbsp;<em>EBioMedicine.</em> <strong>17</strong>, 30-44. PMC5360572.&nbsp;</p>
<p style="text-align: justify;">Samanta D, Guo H, Rubinstein R, Ramagopal UA, Almo SC. (2017) &ldquo;Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2.&rdquo; <em>Mol Immunol</em>. <strong>81</strong>, 51-159. PMC5220579.</p>
<p style="text-align: justify;">Liu W, Ramagopal U, Cheng H, Bonanno JB, Toro R, Bhosle R, Zhan C, Almo SC. (2016) &ldquo;Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.&rdquo; <em>Structure</em> <strong>24</strong>, 2016-2023. PMID:27806260.</p>
<p style="text-align: justify;">Yadava U, Vetting MW, Al Obaidi N, Carter MS, Gerlt JA, Almo SC. (2016) &ldquo;Structure of an ABC transporter solute-binding protein specific for the amino sugars glucosamine and galactosamine.&rdquo; <em>Acta Crystallogr F Struct Biol Commun.</em> <strong>72</strong>, 467-472. PMC4909247.</p>
<p style="text-align: justify;">Liu W, Vigdorovich V, Zhan C, Patskovsky Y, Bonanno JB, Nathenson SG, Almo SC. (2015) &ldquo;Increased Heterologous Protein Expression in Drosophila S2 Cells for Massive Production of Immune Ligands/Receptors and Structural Analysis of Human HVEM.&rdquo; <em>Mol Biotechnol.</em><strong> 57</strong>, 914-922. PMID:26202493.</p>
<p style="text-align: justify;">Kim J, Xiao H, Koh J, Wang Y, Bonanno JB, Thomas K, Babbitt PC, Brown S, Lee YS, Almo SC. (2015) &ldquo;Determinants of the CmoB carboxymethyl transferase utilized for selective tRNA wobble modification.&rdquo; <em>Nucleic Acids Res</em>. <strong>43</strong>, 4602-4613.&nbsp; PMC4482062.</p>
<p style="text-align: justify;">&nbsp;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) &ldquo;Experimental strategies for functional annotation and metabolism discovery: targeted screening of solute binding proteins and unbiased panning of metabolomes.&rdquo; <em>Biochemistry </em><strong>54</strong>, 909-931. PMC4310620.</p>
<p style="text-align: justify;">Samanta D, Almo SC. (2015) &ldquo;Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity.&rdquo; <em>Cell Mol Life Sci</em>. <strong>72</strong>, 645-658. PMID: 25326769.</p>
<p style="text-align: justify;">Liu W, Zhan C, Cheng H, Kumar PR, Bonanno JB, Nathenson SG, Almo SC. (2014) &ldquo;Mechanistic basis for functional promiscuity in the TNF and TNF receptor superfamilies: structure of the LIGHT:DcR3 assembly.&rdquo; <em>Structure</em> <strong>22</strong>, 1252-1262.&nbsp; PMC4163024.</p>
<p style="text-align: justify;">Bandaranayake AD, Almo SC. (2014) &ldquo;Recent advances in mammalian protein production.&rdquo; <em>FEBS Lett.</em> <strong>588</strong>, 253-260. PMC3924552.</p>
<p style="text-align: justify;">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) &ldquo;Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function.&rdquo; <em>Nature </em><strong>498</strong>, 123-126. &nbsp;PMC3895326.</p>
<p style="text-align: justify;">Kim J, Almo SC. (2013) &ldquo;Structural basis for hypermodification of the wobble uridine in tRNA by bifunctional enzyme MnmC.&rdquo; <em>BMC Struct Biol. </em><strong>13:</strong>5. PMC3648344.</p>
<p style="text-align: justify;">Vigdorovich V, Ramagopal UA, L&aacute;z&aacute;r-Moln&aacute;r E, Sylvestre E, Lee JS, Hofmeyer KA, Zang X, Nathenson SG, Almo SC. (2013) &ldquo;Structure and T cell inhibition properties of B7 family member, B7-H3.&rdquo; <em>Structure </em><strong>21</strong>, 707-717. PMC3998375.</p>
<p style="text-align: justify;">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) &ldquo;Crystal structure of human Karyopherin &beta;2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2.&rdquo; <em>J Struct Funct Genomics </em><strong>14</strong>, 31-35. PMC3681870.</p>
<p style="text-align: justify;">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) &ldquo;Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex.&rdquo; <em>Structure </em><strong>21</strong>, 560-571. PMC3755625.</p>