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VERSION:2.0
PRODID:icalendar-ruby
CALSCALE:GREGORIAN
X-WR-CALNAME:Integrated Imaging and Genetic Approaches to Elucidating Islet
  Heterogeneity in Health and Diabetes
X-WR-TIMEZONE:Eastern Time (US & Canada)
BEGIN:VEVENT
DTSTAMP:20260916T155854Z
UID:tag:localist.com\,2008:EventInstance_53373722828335
DTSTART:20260721T120000Z
DTEND:20260721T140000Z
DESCRIPTION:Caroline Ward\, BA - Final Dissertation Defense - HUGEN PhD Can
 didate\n\n \n\nDepartment of Human Genetics Doctoral Candidate\, Caroline 
 Ward\, BA\, will defend the following dissertation on “Integrated Imagin
 g and Genetic Approaches to Elucidating Islet Heterogeneity in Health and 
 Diabetes”\n\n \n\nCOMMITTEE CHAIR: Zachary Z. Freyberg\, MD\, PhD\n\nCom
 mittee Members:\n\nBeth L. Roman\, PhDQuasar S. Padiath\, PhD\, MBBSMichae
 l J. Jurczak\, PhD \n\nABSTRACT:\n\n        \n\n      The pancreatic islet
  is a heterogeneous micro-organ whose cellular composition and signaling v
 ary across cell types\, anatomical location\, sex\, and disease state. Thi
 s dissertation develops complementary strategies to resolve that heterogen
 eity\, first in human type 1 diabetes (T1D) and then in a mouse model of 
 β-cell dopamine signaling.\n\n      In the first study\, an AI-guided who
 le-slide imaging pipeline coupled to a hierarchical Bayesian and mixed-eff
 ects statistical framework was applied to immunohistochemically stained pa
 ncreata from 106 non-diabetic and T1D donors\, quantifying all four endocr
 ine cell types across more than two million islets. T1D produced a coordin
 ated remodeling of islet composition: profound β-cell loss was accompanie
 d by reciprocal α-cell expansion\, whereas δ- and PP-cells were largely 
 resilient. These changes were regionally concentrated\, most pronounced in
  the pancreatic head\, and were modulated by sex\, age\, and disease durat
 ion\, with pseudotime analysis resolving distinct trajectories of composit
 ional change across disease progression.\n\n      The second study examine
 d the contributions of β-cell dopamine D2 receptor (D2R) signaling to gly
 cemic control using a tamoxifen-inducible\, β-cell-specific D2R condition
 al knockout (cKO) mouse model. Loss of β-cell D2R produced sex-dependent 
 metabolic phenotypes: females showed blunted glucose-stimulated insulin se
 cretion and diet-dependent glucose intolerance\, whereas males showed enha
 nced glycemic control and islet secretion. Multiplex RNAscope revealed tha
 t islet D2R is expressed in a subpopulation of β-cells\, suggesting that 
 D2R may contribute to the emerging understanding of β-cell heterogeneity.
 \n\n      Taken together\, both studies highlight important roles for sex 
 differences in β-cell function. Just as importantly\, this work uses comp
 lementary imaging\, genetic\, and physiologic approaches to define distinc
 t populations of endocrine cell types\, both under physiologic and disease
  contexts.\n\n \n\nIN-PERSON EVENT - ALL WELCOME
GEO:40.442113;-79.960776
LOCATION:Biomedical Science Tower\, Conference Room E1695
SUMMARY:Integrated Imaging and Genetic Approaches to Elucidating Islet Hete
 rogeneity in Health and Diabetes
URL;VALUE=URI:https://calendar.pitt.edu/event/integrated-imaging-and-geneti
 c-approaches-to-elucidating-islet-heterogeneity-in-health-and-diabetes
CATEGORIES:Defenses
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