BEGIN:VCALENDAR
VERSION:2.0
PRODID:icalendar-ruby
CALSCALE:GREGORIAN
X-WR-CALNAME:Francisco Garcia Thesis Defense: Molecular Profiling and Mecha
 nisms of Cerebrovascular Function in Health and Neurodegeneration
X-WR-TIMEZONE:Eastern Time (US & Canada)
BEGIN:VEVENT
DTSTAMP:20260616T124541Z
UID:tag:localist.com\,2008:EventInstance_42844287285081
DTSTART:20230414T180000Z
DTEND:20230414T190000Z
DESCRIPTION:Date/Time: Friday\, April 14th at 2PM ET\n\nLocation: MIT\, Sin
 gleton Auditorium 46-3002\n\nZoom Link: https://mit.zoom.us/j/95659169938\
 n\nThesis Title: Molecular Profiling and Mechanisms of Cerebrovascular Fun
 ction in Health and Neurodegeneration\n\nAbstract:\n\nThe unmet medical ne
 ed for therapies that treat neurological disorders is in part due to our l
 ack of understanding the underlying biological mechanisms and inefficient 
 delivery strategies to target the brain. The cerebrovasculature is essenti
 al for proper brain function as it tightly regulates blood flow and suppli
 es the necessary nutrients. Furthermore\, the presence of a blood-brain ba
 rrier (BBB) provides protection to vulnerable neurons but poses a challeng
 e for drug delivery. In neurodegeneration\, BBB breakdown and vascular imp
 airments are hallmarks that precede the onset of disease-specific phenotyp
 es. Efforts to understand the basic biology of cells that comprise the cer
 ebrovasculature as well as the changes that occur in disease have made sig
 nificant progress with the advent of single-cell technologies. Here we cha
 racterize molecular profiles of cell types that comprise the human cerebro
 vasculature using both ex vivo fresh tissue and post mortem in silicosorti
 ng of human brain tissue samples. Using single-nucleus RNA-sequencing (snR
 NA-seq)\, we profile cerebrovascular nuclei across 11 subtypes\, including
  endothelial cells\, mural cells\, and perivascular fibroblasts. We uncove
 r human-specific expression patterns along the arteriovenous axis and dete
 rmine previously uncharacterized cell type-specific markers. Next\, we use
  these human-specific signatures to study changes in cerebrovascular cells
  from patients with Huntington’s disease (HD)\, which reveal activation 
 of innate immune signaling in vascular and glial cell types and a concomit
 ant reduction in the levels of proteins critical for maintenance of blood
 –brain barrier integrity. Lastly\, using a combination of an adeno-assoc
 iated virus (AAV) approach in combination with a cell type-specific promot
 er (CLDN5) towards brain endothelial cells\, we develop an AAV vector for 
 effective gene therapy delivery to the cerebrovasculature. We demonstrate 
 that a single dose of gene therapy targeting the cerebrovasculature to low
 er levels of huntingtin via a microRNA-mediated mechanism is sufficient to
  delay the progression of Huntington’s disease in vivo. Altogether\, thi
 s work provides both a comprehensive molecular atlas for future studies to
  study the cerebrovasculature in health and disease contexts as well as a 
 tool for development of novel therapeutic strategies towards neurological 
 disorders.
GEO:42.362302;-71.091766
LOCATION:Singleton Auditorium\, 46-3002
SUMMARY:Francisco Garcia Thesis Defense: Molecular Profiling and Mechanisms
  of Cerebrovascular Function in Health and Neurodegeneration
URL;VALUE=URI:https://calendar.mit.edu/event/francisco_garcia_thesis_defens
 e_molecular_profiling_and_mechanisms_of_cerebrovascular_function_in_health
 _and_neurodegeneration
CATEGORIES:Thesis defense
END:VEVENT
END:VCALENDAR