Research

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Immune cells are privileged with high plasticity to enable them cope with quickly changing environmental cues and contexts. Hakeem Lab focuses on studying differentiation of T lymphocytes under different contexts of acute infection and chronic diseases.

In the context of chronic diseases, such as cancer and chronic viral infection,  T lymphocytes become progressively dysfunctional, and adopt a unique differentiation program, usually know as exhausted T cells (Tex). Immunotherapy has revolutionized cancer treatment by enhancing the immune system, specifically reinvigorating Tex cells.  

One main research focus in Hakeem Lab is studying the different factors modulating the epigenetic landscapes of exhausted T cells (Tex), using both mouse models and human samples.

Some of our specific aims include:

1- Studying the effect of different cytokines on modulating Tex phenotypically, transcriptionally, and epigenetically, as well as how these modulations reflect functionally.

2- Identification of previously underappreciated pathways of specific interest in the development of T-cell exhaustion.

3- Mapping transcriptional and epigenetic networks involved in recovery from T-cell exhaustion.

4- The potential action of specific interventions that reverse the dysfunctional state associated with Tex and have the potential of reversing T-cell exhaustion.

Another main research direction in Hakeem Lab is dissecting the "bystander" effect of preexisting exhaustion milieu on the transcriptional, epigenetic, and proteomic profiles of T cells responding to acute infection and vaccination. We performed proof-of-concept studies using acute infection with Listeria monocytogenes in the presence of preexisting chronic infection with LCMV-Clone13.