Daniel Kober, Ph.D. Assistant Professor Endowed Title W.W. Caruth, Jr. Scholar in Biomedical Research School Medical School Department Biochemistry Graduate Programs Biological Chemistry, Molecular Biophysics Biography Download Curriculum Vitae Dan joined the faculty at UTSW in the fall of 2022 as an Assistant Professor. His lab in the Department of Biochemistry studies the biochemical and biophysical basis for the regulation of lipid metabolism through targeted protein degradation. Dan earned his B.S. from Evangel University in Springfield, MO in 2012. He received his Ph.D. from Washington University in St. Louis in 2017. There, he trained under Tom Brett and studied the biophysical basis for disease-linked mutations in the neuroimmune receptor, TREM2. As a postdoctoral fellow, Dan trained at UTSW with Dan Rosenbaum and Arun Radhakrishnan, where he began his journey into lipid metabolism through the cholesterol-regulating Scap-SREBP pathway. He uncovered a new role for degradation of the precursor form of the lipogenic transcription factor protein, SREBP2. He used cryo-electron microscopy to visualize the high and low cholesterol conformations of Scap, the key cholesterol sensor in the ER. Dan’s independent lab continues this interest in understanding the interplay between protein degradation and lipid metabolism. Dan has received several awards for his research. As a graduate student, he received two fellowships from the American Heart Association. As a postdoc, he received a fellowship from the American Heart Association as well as a K99/R00 NIH Pathway to Independence Award. As in incoming Assistant Professor, he received a UT Systems Rising STARs Award and joined the Department of Biochemistry as an Endowed Scholar. Research Interest Lipid metabolism Membrane protein structural biology Proteases and inhibitors Protein homeostasis and degradation Publications Featured Publications Structures of the multi-domain oxygen sensor DosP: remote control of a c-di-GMP phosphodiesterase by a regulatory PAS domain. Wu W, Kumar P, Brautigam CA, Tso SC, Baniasadi HR, Kober DL, Gilles-Gonzalez MA, Nat Commun 2024 Nov 15 1 9653 SPRING licenses S1P-mediated cleavage of SREBP2 by displacing an inhibitory pro-domain. Hendrix S, Dartigue V, Hall H, Bawaria S, Kingma J, Bajaj B, Zelcer N, Kober DL, Nat Commun 2024 Jul 15 1 5732 Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing. Kober DL, Radhakrishnan A, Goldstein JL, Brown MS, Clark LD, Bai XC, Rosenbaum DM, Cell 2021 Jun Identification of a degradation signal at the carboxy terminus of SREBP2: A new role for this domain in cholesterol homeostasis. Kober DL, Xu S, Li S, Bajaj B, Liang G, Rosenbaum DM, Radhakrishnan A, Proc Natl Acad Sci U S A 2020 Oct Development of a monoclonal antibody to study MARCH6, an E3 ligase that regulates proteins that control lipid homeostasis. Xu S, Donnelly L, Kober DL, Mak M, Radhakrishnan A, J Lipid Res 2024 Sep 100650 Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo. Kober DL, Caballero Van Dyke MC, Eitson JL, Boys IN, McDougal MB, Rosenbaum DM, Schoggins JW, mBio 2024 May e0076824 SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P. Hendrix S, Tan JME, Ndoj K, Kingma J, Valiloo M, Zijlstra LF, Ottenhoff R, Seidah NG, Loregger A, Kober DL, Zelcer N, Mol Cell Biol 2024 44 4 123-137 Functional insights from biophysical study of TREM2 interactions with apoE and A?1-42. Kober DL, Stuchell-Brereton MD, Kluender CE, Dean HB, Strickland MR, Steinberg DF, Nelson SS, Baban B, Holtzman DM, Frieden C, Alexander-Brett J, Roberson ED, Song Y, Brett TJ, Alzheimers Dement 2020 Oct YbtT is a low-specificity type II thioesterase that maintains production of the metallophore yersiniabactin in pathogenic enterobacteria. Ohlemacher SI, Xu Y, Kober DL, Malik M, Nix JC, Brett TJ, Henderson JP, J Biol Chem 2018 12 293 51 19572-19585 Limiting Respiratory Viral Infection by Targeting Antiviral and Immunological Functions of BST-2/Tetherin: Knowledge and Gaps. Berry KN, Kober DL, Su A, Brett TJ, Bioessays 2018 10 40 10 e1800086 Results 1-10 of 17 1 2 Next Last Honors & Awards K99 Pathway to Independence Award (2021) American Heart Association Post-Doctoral Fellowship (2018-2020) Helmsley Scholarship for CSHL Cryo-EM course (2018) American Heart Association Pre-Doctoral Fellowship (2017) American Heart Association Pre-Doctoral Fellowship (2015-2017)