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Shukti Chakravarti, Ph.D.
Shukti Chakravarti, Ph.D.
Primary Appointment: Department of Medicine, Gastroenterology
Johns Hopkins University School of Medicine
720 Rutland Avenue, 935 Ross
Baltimore, MD 21205
Research Title: Extracellular matrix and tissue homeostasis
The Shukti Chakravarti Laboratory is interested in the regulation of cellular functions and tissue homeostasis by the extracellular matrix (ECM). The laboratory investigates functions of collagen-associated extracellular matrix proteins and proteoglycans, lumican, fibromodulin and biglycan in maintaining connective tissue architecture and cellular functions. Lumican regulates collagen fibril structure such that gene targeted mice deficient in lumican manifest Ehlers Danlos Syndrome-like skin fragility, tendon weaknesses and corneal opacity. These ECM proteins also regulate host innate immune responses by interacting with toll-like receptor (TLR) signals to promote sensing of pathogen-associated molecular patterns, or presenting as danger signals themselves. Our investigation of the ECM centers on two barrier tissues, the cornea of the eye and the intestinal mucosa and submucosa.
Inflammatory Bowel Diseases (IBD): Crohn’s disease and ulcerative colitis are two major IBD types. Our works have identified gene expression patterns of these two types of IBD from surgical specimens and endoscopic pinch biopsies. We have developed a mouse model of chronic colitis using trinitrobenzene sulfonic acid, and by microarray gene expression profiling of the mouse colon at the early and late stages of colitis investigated inflammatory and fibrosis-related genes. Using a few different mouse models of IBD and the proteoglycan knockout mice, we are now investigating how the ECM proteoglycans regulate immune cell functions in the intestine.
Corneal infection and inflammation studies: The cornea is an avascular specialized type of barrier tissue that maintains an immune privileged status through an active innate and restricted adaptive immune response. Our goals are to understand how corneal proteoglycans regulate innate and adaptive immune responses in the context of infections and wound healing. Lumican interacts with CD14 that conveys bacterial lipopolysaccharides to TLR4 and promotes induction of pro-inflammatory cytokines and phagocytosis of gram-negative bacteria.
We are also investigating the role of four antimicrobial peptidoglycan recognition proteins in corneal host defense.
Keratoconus: This is a thinning ectatic disease of the cornea that affects 1 in 2000 individuals within their first two decades of life. It is progressive, vision-disruptive, and without a cure, it is the leading cause for cornea transplantation. Keratoconus is a complex disease that is regulated by multiple genes and environmental factors. We are investigating keratoconus pathophysiology using multiple approaches. Contributions of specific genes are being sought by a) exome sequencing of DNA from patient blood, b) differential transcriptome and proteome of corneal tissues. We have established primary cells from keratoconus corneas to examine features of the disease in culture.