The Molecular Immunology Section studies mechanisms of gene regulation, focusing on the innate immune system.

The section is affiliated with and provides expertise in gene regulation to the Cancer Innovation Laboratory of the National Cancer Institute Center for Cancer Research. 

Role of innate immune system and its potential applications to cancer treatment 

A large portion of modern cancer research focuses on the ability of the immune system to destroy cancer cells using tumor-specific antibodies and immunomodulatory agents. We seek to better understand the cellular and molecular mechanisms of natural killer (NK) cell development and function to ultimately design novel antitumor therapies.  

Understanding natural killer cells 

Our work provides insight into the mechanisms of NK cell development, as well as a method to identify individuals with high NK activity, that may provide superior outcomes in hematopoietic stem cell transfer.  

Impact on cell fate

Data show alternative cell fates generated by promoter competition

18% of transcription factor genes possess divergent and convergent promoter pairs.
Implications for stem cell transfer

Identification of NK-cell-specific system regulating HLA-C expression

Study indicates an important role for HLA-C in the development and function of NK cells.

Role of intronic antisense promoters 

Our research demonstrated that intronic antisense promoters act as “off” switches in lineage-determining transcription factors. To follow up on this discovery, we are deleting the antisense promoters from several transcription factors to test the hypothesis that antisense transcription limits the frequency of differentiation toward the lineage dictated by a given transcription factor.  

Our capabilities and specializations

Natural killer cell gene regulation 

Natural killer cells serve a vital role in the innate immune response. Therefore, we investigate their gene regulation.

  • Determining the molecular mechanisms controlling variegated expression of human KIR genes and mouse Ly49 genes 

  • Analyzing NK-specific regulation of the human HLA-C gene 

Investigate properties of binary switch promoters 

We investigate binary switches and their properties, exploring the hypothesis that bidirectional promoters can digitally program cellular development and differentiation pathways.

  • Evaluating promoters of lineage-defining transcription factors with the potential to function as a binary switch 

Provide expertise in the study of gene regulation to collaborators 

We leverage our expertise to support intramural and extramural collaborators by identifying important regulatory elements and conducting specialized experiments and analysis.

  • Promoter reporter assays 

  • Gel-shift experiments 

  • RNA-seq and other next-generation datasets