Jody Baron, MD, PhD

Associate Professor
Department of Medicine
+1 415 476-5728
Research Overview: 

Our research group studies basic mechanisms involved in immunopathogenesis of acute and chronic Hepatitis B virus infection, as well as basic principles in both innate and adaptive immunity to viral pathogens. By identifying the role of both innate and adaptive immunity in HBV clearance and virus-induced liver damage, we hope to develop strategies for therapeutic intervention.

Hepatitis B virus (HBV) is a partially double?stranded DNA virus that causes acute and chronic hepatitis in humans. Although the majority of infected individuals generate an immune response leading to viral clearance without long-term sequelae, up to 5% of infected adults (and over 90% of exposed neonates) will develop chronic infection and chronic hepatitis. HBV replication itself is not cytopathic, and evidence has shown that hepatic pathology is immune-mediated. Natural hepadnaviral infections occur only in humans and other species whose immune systems vary from individual to individual (outbreeding), thus making it difficult to study immunopathogenesis. Therefore, the experimental study of HBV immunopathogenesis has been limited.

We have now developed a novel transgenic mouse system that models the immune response that would occur in a natural primary Hepatitis B Virus infection. This model has potential to investigate both basic mechanisms involved in immunopathogenesis of acute and chronic virus infection such as hepatitis B virus, as well as basic principles in both innate and adaptive immunity to viral pathogens. Our experiments seek to use and extend this model to identify the mechanisms involved in this acute and chronic hepatitis with the long term goal of developing a more comprehensive understanding of the role of both innate and adaptive immunity in HBV clearance and virus-induced liver damage. In addition, our results provide evidence for the first in vivo function for a population of innate-like lymphocytes whose function is not well understood (Natural Killer T lymphocytes or NKT cells). Therefore, our model also allows us a unique opportunity to understand the function, ligands, and regulation of these unusual lymphocytes and their restriction element, the MHC class I-like molecule, CD1d.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Virology & Microbial Pathogenesis
Research Summary: 
Innate and adaptive immunity to viral pathogens

Websites

Publications: 

Cryo-EM Reveals Integrin-Mediated TGF-ß Activation without Release from Latent TGF-ß.

Cell

Campbell MG, Cormier A, Ito S, Seed RI, Bondesson AJ, Lou J, Marks JD, Baron JL, Cheng Y, Nishimura SL

Integrin αvβ8-expressing tumor cells evade host immunity by regulating TGF-β activation in immune cells.

JCI insight

Takasaka N, Seed RI, Cormier A, Bondesson AJ, Lou J, Elattma A, Ito S, Yanagisawa H, Hashimoto M, Ma R, Levine MD, Publicover J, Potts R, Jespersen JM, Campbell MG, Conrad F, Marks JD, Cheng Y, Baron JL, Nishimura SL

Cryo-EM structure of the αvβ8 integrin reveals a mechanism for stabilizing integrin extension.

Nature structural & molecular biology

Cormier A, Campbell MG, Ito S, Wu S, Lou J, Marks J, Baron JL, Nishimura SL, Cheng Y

An OX40/OX40L interaction directs successful immunity to hepatitis B virus.

Science translational medicine

Publicover J, Gaggar A, Jespersen JM, Halac U, Johnson AJ, Goodsell A, Avanesyan L, Nishimura SL, Holdorf M, Mansfield KG, Judge JB, Koshti A, Croft M, Wakil AE, Rosenthal P, Pai E, Cooper S, Baron JL