Susanne M. Cabrera, MD
Associate Professor, Pediatrics (Endocrinology)
- Pediatrics (Endocrinology)
Residency, Internal Medicine and Pediatrics, Indiana University, Indianapolis, IN, 2009
Fellowship, Pediatric Endocrinology, Indiana University, Indianapolis, IN, 2011
- Slam Dunk for Diabetes Camp
The accurate prediction of type 1 diabetes occurrence by combining markers of beta cell dysfunction with heightened pro-inflammatory profiles
The overall goal of my research is to better predict those at risk of developing type 1 diabetes by combining early markers of beta cell dysfunction with specific pro-inflammatory profiles seen in those both progressing to T1D and in family members of those already affected with T1D, ultimately translating this mechanistic knowledge into clinical trials aimed at preventing T1D. This work builds off the existing and extensive research on molecular signatures in the longitudinal bio-bank of those affected with T1D and their family members by the McGee Center. Analysis of the inflammatory profiles of those progressing to T1D reveals a distinctive and predictive profile highlighted by a loss of regulation and a movement towards heightened inflammation. To improve these signatures as a predictive tool, I hope to link evidence of early beta cell dysfunction to the immune dysregulation. My hypothesis is that innate beta cell dysfunction is a necessary and critical for advancing this inflammation forward to clinical overt T1D.
I was fortunate to work in the lab of Dr. Raghu Mirmira, a beta cell biologist and physician-scientist, during my fellowship training in pediatric endocrinology at Indiana University. There, I researched the combined beta-cell and immune effects of several drugs in the non-obese diabetic mouse (a model of type 1 diabetes). This experience was critical in allowing me to bridge the gap between beta cell dysfunction and the immune response in T1D pathogenesis. Indeed, since joining the faculty at MCW, I have been active in the McGee Center investigating evidence of beta cell dysfunction in both low and high risk family members of those with T1D.
I am also researching the effect of a low antigen diet on decreasing gut hyper-permeability, systemic inflammation, and thus protecting beta cell function in the bio-breeding rat (a model of T1D). We believe endotoxin is a key player in driving the inflammatory response seen in those at risk of T1D, and that endotoxin exposure can be reduced by decreasing gut hyperpermeability through a low antigen diet. Early results suggest the decrease in gut hyperpermeability results in improved beta cell function.
Clinically, I am involved with the TrialNet Natural History study and the McGee Center’s Genetics of Autoimmunity in Type 1 Diabetes Mellitus, a longitudinal study of family members of those affected by T1D. My on-going clinical obligations to children and teens with T1D provide a wealth of potential subjects for recruitment (> 200 children are newly diagnosed through our Diabetes Center at MCW annually, over 1700 patients with T1D cared for in our Diabetes Clinic), and a valuable understanding of the morbidity associated with T1D. I am also a Clinical Research Scholar through the CTSI at MCW, an NIH supported program aimed at advancing the research careers of young investigators by securing extramural funding and providing a supportive framework.
(Cabrera SM, Engle S, Kaldunski M, Jia S, Geoffrey R, Simpson P, Szabo A, Speake C, Greenbaum CJ, Type 1 Diabetes TrialNet CTLA4-Ig (Abatacept) Study Group, Chen YG, Hessner MJ.) Diabetologia. 2018 11;61(11):2356-2370.
(Henschel AM, Cabrera SM, Kaldunski ML, Jia S, Geoffrey R, Roethle MF, Lam V, Chen YG, Wang X, Salzman NH, Hessner MJ.) PLoS One. 2018;13(1):e0190351.
(Fawley J, Koehler S, Cabrera S, Lam V, Fredrich K, Hessner M, Salzman N, Gourlay D.) J Surg Res. 2017 10;218:35-42.
(Cabrera SM, Wang X, Chen YG, Jia S, Kaldunski ML, Greenbaum CJ, Type 1 Diabetes TrialNet Canakinumab Study Group, Mandrup-Poulsen T, AIDA Study Group, Hessner MJ.) Eur J Immunol. 2016 Apr;46(4):1030-46.
(Cabrera SM, Chen YG, Hagopian WA, Hessner MJ.) Diabetologia. 2016 Mar;59(3):414-25.
(Cabrera SM, Henschel AM, Hessner MJ.) Transl Res. 2016 Jan;167(1):214-27.
(Fisher MM, Cabrera SM, Imel EA.) Endocrinol Diabetes Metab Case Rep. 2015;2015:150040.
(Chen YG, Cabrera SM, Jia S, Kaldunski ML, Kramer J, Cheong S, Geoffrey R, Roethle MF, Woodliff JE, Greenbaum CJ, Wang X, Hessner MJ.) Diabetes. 2014 Nov;63(11):3960-73.
(Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA.) J Pediatr Endocrinol Metab. 2014 Jan;27(1-2):47-51.
(Cabrera SM, Colvin SC, Tersey SA, Maier B, Nadler JL, Mirmira RG.) Clin Exp Immunol. 2013 Jun;172(3):375-82.
(Cabrera SM, Rogol AD.) Expert Opin Drug Saf. 2013 May;12(3):375-88.
(Narala B, Cabrera SM.) The 5-Minute Pediatric Consult, 8th Edition. 1 January 2018:844-845.