Why genetics?

1 . Identifying novel therapeutic strategies

We and other geneticists have developed bioinformatic and statistical algorithms that distinguish driver events from passenger events. By identifying the molecular programs that are necessary for disease pathogenesis, we can rationally identify therapeutic strategies that target disease.

As an example, we have utilized genetics to identify a gain-of-function mutation in an immunological disease (hypereosinophilic syndrome). This genetic analysis implicated the JAK-STAT pathway as a driver event in HES (Walker, et al., 2016). We have utilized these data to propose that JAK-STAT inhibitors are an effective therapeutic strategy for this disease (King, et al., 2017).

2. Elucidating fundamental biology.

There are approximately between 20,000 and 25,000 genes. Only ~10,000 are described in 10 or more articles in Pubmed. To identify the function of the remaining genes, we are using human genetics. To date, we have implicated novel mutations in CD28, RHOA, CSNK1A1, RLTPR, and other genes in CTCL and related diseases. These mutations provide novel insights into T cell physiology and lymphomagenesis.

We are currently utilizing these approaches to identify novel disease-promoting mutations in CTCL and other diseases. These mutations promise to implicate novel genes and noncoding regions in human health and disease.

3. Development of novel technologies.

Our lab has expertise in genome-wide genetic screens, next generation sequencing, and statistical approaches. We are utilizing these expertise to develop novel technologies. In progress!