Rajagopal, Lakshmi

Faculty Profile

First Name: 
Lakshmi
Last Name: 
Rajagopal
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Title: 
Associate Professor
Primary Institution: 
UW
Department/Division: 
other
Department/Division: 
Global Health
Mail/Box #: 

356320

Office Location: 

Seattle Children's Hospital Research Institute, 1900 Ninth Avenue, Seattle, WA 98101-1304

Office Phone: 
(206) 884-7336
Research

Research Summary: 

Our research interest is to understand signaling events and gene regulation that are critical for bacterial disease pathogenesis. The human pathogens that we study are Group B Streptococcus (GBS) and Staphylococcus aureus. Although both GBS and S. aureus are commensal organisms, these bacteria can also become disease-causing pathogens. GBS are commonly found in the recto-vaginal tract of healthy women but can cause severe invasive disease in human newborns and adults including the elderly, immuno-compromised and diabetic individuals. GBS disease commonly manifests as pneumonia, sepsis and meningitis. Our studies on GBS are focused on understanding how these bacteria adapt to the environmental niches encountered during their life cycle. Studies from our research have shown that GBS encodes signaling factors such as a serine/threonine kinase regulates the expression of  toxins and also enables the bacteria to adapt to nutrient starvation. We have demonstrated that the kinase affects toxin expression based upon its interaction with a DNA-binding response regulator known as CovR. The interaction between the kinase and CovR represents novel findings in bacterial environmental adaptation.  More recently, we have shown that GBS mutants defective for CovR signaling show increased blood brain barrier penetration and thus provide insight into how the organism can transition from a commensal organism to a virulent, meningeal pathogen. Current research is focused toward identifying the environmental cues/signals that are sensed by these bacteria for regulation of toxins and understanding how the pathogen migrates through different host cells during infections.S. aureus are also Gram-positive bacteria that can cause severe invasive disease in humans. Infections due to S. aureus include deep seated infections such as bacteremia, sepsis, pneumonia, ostemolyelitis and toxic shock syndrome. In the U.S, infections caused by methicillin resistant strains of S. aureus (MRSA) are have even surpassed numbers linked to HIV/AIDS. We have recently identified a number of novel genes/signaling factors that regulate antibiotic resistance, toxin expression and S. aureus virulence. Current studies are focused on elucidating how these signaling factors affect antibiotic resistance and S. aureus infections such as sepsis and pneumonia. We are also investigating how mutations in host signaling pathways affect disease suceptibility to S. aureus. This is particularly relevant as patients with genetic disorders such as Jobs Syndrome and Chronic granulomatous disease (CGD) are prone to recurrent and life threatening infections due toS. aureus. The ultimate goal is to use the information gathered from our research to identify novel compounds that can be used to treat these bacterial infections.

Short Research Description: 
Understanding bacterial disease pathogenesis
Areas of Interest: 
Microbiology, Infection & Immunity
Keywords: 
<p> Infectious Disease, Bacterial Pathogenesis, Gram positive bacteria, Signal Transduction, Gene Expression, Group B Streptococcus, Staphylococcus aureus,Innate Immunity</p>
Publications


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