Daniel Kober, Ph.D.

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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.  

• Lipid metabolism
• Membrane protein structural biology
• Protein homeostasis and degradation

Featured Publications

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

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

TREM2-Ligand Interactions in Health and Disease.

Kober DL, Brett TJ, J Mol Biol 2017 06 429 11 1607-1629

First comprehensive structural and biophysical analysis of MAPK13 inhibitors targeting DFG-in and DFG-out binding modes.

Yurtsever Z, Patel DA, Kober DL, Su A, Miller CA, Romero AG, Holtzman MJ, Brett TJ Biochim. Biophys. Acta 2016 Nov 1860 11 Pt A 2335-44

Efficient Mammalian Cell Expression and Single-step Purification of Extracellular Glycoproteins for Crystallization.

Kober DL, Yurtsever Z, Brett TJ, J Vis Exp 2015 Dec 106 e53445

TREM-2 promotes macrophage survival and lung disease after respiratory viral infection.

Wu K, Byers DE, Jin X, Agapov E, Alexander-Brett J, Patel AC, Cella M, Gilfilan S, Colonna M, Kober DL, Brett TJ, Holtzman MJ, J Exp Med 2015 May 212 5 681-97

Preparation, crystallization, and preliminary crystallographic analysis of wild-type and mutant human TREM-2 ectodomains linked to neurodegenerative and inflammatory diseases.

Kober DL, Wanhainen KM, Johnson BM, Randolph DT, Holtzman MJ, Brett TJ, Protein Expr Purif 2014 Apr 96 32-8

• 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)