MD

Benjamin  Enslow

MD

Microbiology, Immunology, and Molecular Genetics

Mentor:  Dr. Elizabeth Leadbetter

Phone:  (830) 391-4298

Email:  enslow@uthscsa.edu

ORCID iD:  https://orcid.org/0000-0003-4822-0216

I have had the privilege and pleasure of obtaining a diverse background in the biomedical sciences, basic and translational research, and health care. I earned my bachelors in science in Biochemistry with honors from Schreiner University in Kerrville, Tx, and my MD from the Long School of Medicine at UT Health San Antonio. While there, in addition to studying the human body, physiology, and disease states, I began pursuing  what would become a career-altering fascination with cellular signaling.

     In addition to completing my clinical responsibilities and coursework as a medical student, I began a “ground-up” approach to biomedical research. I began involving myself in work grounded in the biophysical and biochemical fundamenals of ion channels, and over time, graduated to the study of  organellar and cell biology (mitochondrial and cytoskeletal dynamics as well as cancer pharmacology), in vivo studies of disease states (obesity, metabolic disorders and NAFLD/NASH/HCC), and lastly, clinical research that focused on novel therapeutic interventions for the treatment of pediatric acute liver failure of indeterminate origin. I began my first year as a postdoctoral fellow while under a TL1 Translational Science Training grant while studying molecular mechanisms of liver and kidney function, primary in the areas of metabolism and cellular bioenergetics. My experiences studying translational science, along with my love for guest lecturing and mentoring undergraduates in the laboratory led me towards choosing education as a primary career path, and I sought and obtained a fellowship in the Saber-IRACDA K12 Postdoctoral Training program by the end of my first year. 

    My current research focus is on immunometabolism with respect to liver disease, and my long term career goals are as follows:  1) to devleop a pedogogical philosophy that will allow me to help connect the ideas and concepts that undergraduates are learning at their level with larger research movements, and 2) train, foster, and preserve, their innate ability to think about science not only critically, but "translationally". Ultimately, I think this will allow future researchers and practitioners to be more effective at navigating the road from bench-to-bedside and better cement their understanding of the immediate material in front of them.

Education

2014 BS (Biochemistry) Schreiner University
2019 MD Long School of Medicine (UT Health San Antonio)

Research

Description: Nonalcoholic Fatty Liver Disease (NAFLD) is a widespread and growing problem both in the United States and abroad. The cellular and molecular mechanisms by which NAFLD progresses to steatosis (NASH), cirrhosis, and in some cases, hepatocellular carcinoma (HCC) are ill-defined. Within the liver, numerous immunologic cells of both the innate and adaptive immune systems have been implicated in the development and progression of NAFLD. However, much is still lacking in terms of the mechanisms behind dysregulated hepatocyte-immune cell interactions, especially concerning intrahepatic invariant chain natural killer T (iNKT) cells. In my project, I seek to both define and characterize the immunophenotypic changes within the liver in various murine models of obesity, NAFLD, NASH, and HCC. A particular focus will be on the changing frequencies and activation states of iNKT cells, and subpopulations of intrahepatic B cells.  Additionally, it is known that the MHC1-like antigen-presenting molecule CD1d is necessarily glycosylated in order to be expressed at the surface of antigen-presenting cells (including hepatocytes and B cells). Therefore, in this study, proposed defects involving the magnesium- and calcium-dependent molecular machinery involved in the process of N-linked glycosylation, secondary to increased lipotoxicity, will be also be evaluated. My central hypothesis is that steatosis and lipotoxicity within the hepatocyte results in ER stress that negatively impacts the function and/or expression of components of the oligosaccharyltransferase (OST) complex, leading to downregulation of CD1d on the cell surface. As a consequence of CD1d downregulation, I propose that iNKT cells are lead to adopt a pro-inflammatory response, promoting changes in intrahepatic lymphocyte frequencies and activation states, culminating in an increasing, and chronic, inflammatory condition. This mechanism, I predict, contributes to the progression of NAFLD to NASH and HCC. This hypothesis will be tested using both cellular immunologic techniques (such as multiplex flow cytometry, in vitro and ex vivo co-culture cellular activation assays, and ELISAs), as well as molecular biology technologies and approaches (confocal microscopy, RNAi-mediated genetic silencing/deletion, IHC/IF, Western blotting, and RT-PCR). 

Honors

2019-2020 (TST) TL1 Translational Science Postdoctoral Scholar (NCATS TL1 TR002647)
2020 Blue Ribbon Abstract Award Winner, Association for Clinical and Translational Science (ACTS) Annual Meeting; 2020 April 15-16; Washington, DC
2020-Present Saber-IRACDA K12 Program Scholar (Year 1)

Publications

  • Nemani N, Dong Z, Daw CC, Madaris TR, Ramachandran K, Enslow BT, Rubbannelsonkumar CS, Shanmughapriya S, Mallireddigari V, Maity S, SingMalla P, Kalimuthusamy N, Hooper R, Shannon CE, Tortellotte WG, Reeves WB, Sharma K, Norton, L, Srikantan S, Soboloff J, Madesh M. (2020). Mitochondrial Pyruvate and Fatty Acid Flux Modulate MICU-1 Dependent Control of MCU Activity. Science Signaling. doi: 10.1126/scisignal.aaz6206  

 

  • Archer CR, Enslow BT, Carver CM, Stockand JD. (2020). Phosphatidylinositol 4,5-biphosphate Directly Interacts with the beta and gamma Subunits of the Sodium Channel ENaC. J Biol Chem. doi: 10.1074/jbc.ra120.012606

 

  • Enslow BT, Stockand JD, Berman JM. (2019). Liddle Syndrome: Mechanisms, Diagnosis, and Management. Integr Blood Press Control. doi: 10.2147/IBPC.S188869

 

  • Huang Y,  Zhiliang L Risinger AL,  Enslow BT,  Zeman CJ, Gong J, Yang Y, Schanze KS. (2019). Fluorescence Spectral Shape Analysis for Nucleotide Identification. PNAS. doi:10.1073/pnas.1820713116

 

  • Archer CR, Enslow BT, Taylor AB, De la Rosa V, Bhattacharya A, Shapiro MS. (2019). A Mutually Induced Conformational Fit Underlies Ca2+-directed Interactions Between Calmodulin and the Proximal C Terminus of KCNQ4 K+ Channels. J Biol Chem. doi:10.1074/jbc.RA118.006857
    • Crystal Structure: PDB: 6N5W