Current Projects

Trim Project

Trim-directed autophagy in hiv restriction and control of inflammation

Project Leader: Michael Mandell

Members of the TRIM family of proteins have been identified as being capable of limiting the ability of HIV to infect and replicate within cells, but the mechanism(s) underlying their action have not been fully uncovered. In this proposal, we test the hypothesis that autophagy, a pathway that can be manipulated with existing drugs, underlies the action of TRIM proteins in antiviral defense. These studies will further our understanding of the cellular functions of TRIM proteins at a molecular level and may provide the groundwork for therapeutic approaches to the diverse diseases, including HIV/AIDS, in which TRIMs play a role.

T-Helper Project

Regulation of beige fat development by mtorc1 and autophagy

Project Leader: Meilian Liu

Brown and brown‐like (beige or brite) adipocytes in adipose tissue have strong anti‐obesity and anti‐ diabetic benefits. However, the mechanisms underlying the browning of white adipose tissue remains largely unknown. This proposed study investigates how mTORC1 and autophagy pathways cooperate to regulate the recruitment and activation of beige adipocytes in white adipose tissue. The results from this study may lead to the identification of potential therapeutic targets for the treatment of obesity and its associated metabolic diseases.

T-Helper Project

Unfolded protein response and autophagy in t helper cell effector function

Project Leader: Xuexian Yang

The function of T helper (TH) cells, the central organizers of adaptive immunity, is specified by the effector cytokines they produce. Regulation of TH cell cytokine secretion is not well understood and represents an important gap in our knowledge. In our preliminary studies, we found that in vitro, deficiency of membrane-associated nucleic acid binding protein (Mnab) led to profound defects in TH cell effector cytokine production. How Mnab regulates TH cell effector function is entirely unclear. We hypothesize that Mnab modulates stability of mRNAs encoding proteins in a common pathway that is critical in TH cell cytokine production. Our current data support a novel hypothesis that Mnab stabilizes mRNAs in the stress response-autophagy pathway that is required for secretory cells. In the proposed study, we will further understand how Mnab controls TH cell cytokine secretion and whether Mnab regulates TH cell function in disease models. Our studies will reveal a novel post-transcriptional control mechanism of TH cell effector function. Manipulation of the corresponding pathways may be of therapeutic benefit in human disease, such as autoimmune and inflammatory disorders.

GCN4 and ATF4 Pathway

Investigating the Role of Autophagy and Other Downstream Effectors in Lifespan Extension by the GCN4/ ATF4 Pathway

Project Leader: Mark McCormick

Pilot Projects

T-Helper Project

Autophagic Control of Interleukin-12 and IL-12-mediated Inflammation

Project Leader: Eliseo Castillo
T-Helper Project

Dissecting the Differential Effect of VCP Inhibitors on Autophagy and VCP Activity

Project Leader: Jeremy Chien
T-Helper Project

Cyclic Nucleotides Efflux and Autophagy in AML

Project Leader: Alexandre Chigaev
T-Helper Project

A Double-Blind, Placebo-Controlled Trial of Anti-Aging, Pro-Autophagy Effects of Metformin in Adults with Prediabetes

Project Leader: Mark Burge (CTSC)
T-Helper Project

Autophagy Plays Diverse Roles in Different Phases of Ischemic Stroke

Project Leader: Rong Pan
Dr.Tom Byrd

Characterization of the T helper cell phenotype in patients with bronchiectasis and its influence on Mycobacterium abscessus xenophagy

Project Leader: Thomas Byrd, MD
Other Projects
T-Helper Project

Regulation of intestinal tight junction barrier and inflammation by autophagy

Project Leader: Prashant Nighot
Graduated; Received an independent R01; Completed January 2018

Brown and brown‐like (beige or brite) adipocytes in adipose tissue have strong anti‐obesity and anti‐diabetic benefits. However, the mechanisms underlying the browning of white adipose tissue remains largely unknown. This proposed study investigates how mTORC1 and autophagy pathways cooperate to regulate the recruitment and activation of beige adipocytes in white adipose tissue. The results from this study may lead to the identification of potential therapeutic targets for the treatment of obesity and its associated metabolic diseases.