Molecular mechanisms underlying Idiopathic pulmonary Fibrosis 

Idiopathic pulmonary fibrosis (IPF) is the most severe idiopathic interstitial lung disease, affecting more than 50,000 Americans each year. While there are a small number of treatment options available, only a moderate impact on disease progression is obtained. Unfortunately, the majority of patients will die from respiratory failure within 3-5 years from the initial diagnosis. Currently, our understanding of the cell types and molecular mechanisms underlying IPF remain limited. To this end, our group has formed a collaboration with Dr. Jonathan Kropski (Vanderbilt University), Dr. Ross Bremner (Dignity Health), and Dr. Rajat Walia (Dignity Health) to characterize the gene regulatory architecture of IPF and healthy lungs at the single cell resolution. This work will provide critical information for understanding IPF biology and developing novel treatment strategies. 

This work is supported by the NHLBI and the Department of Defense.

in Multiple myeloma

Multiple myeloma (MM) is the second most common hematological cancer, accounting for roughly 2% of all cancer deaths. The past decade has brought about a number of new treatment options, drastically increasing the survival of patients. Unfortunately, MM remains incurable and nearly all patients experience relapse. Thus, understanding the complex cancer phenotypes, such as disease progression and treatment response, is critical for progression toward better treatment of MM. However, the molecular mechanisms underlying these phenotypes are often poorly understood. The vast majority of work in this area has focused on identifying mutations disrupting the protein coding portion of the genome that affect these phenotypes. While there have been great successes, it is clear protein coding mutations alone cannot explain the observed variation in complex cancer phenotypes. To this end, the Banovich lab is exploring how changes in gene expression, driven by non-coding variation (somatic and germline), can alter these phenotypes in MM. Our work is focused in two areas: 1) We are using the Multiple Myeloma Research Foundation CoMMpass study to computationally identify non-coding variation associated with complex cancer phenotypes and 2) We are using high throughput CRISPR/Cas9 screens in vitro to identify loci associated with tumor survival and growth. This work is in collaboration with Dr. Jonathan Keats, Dr. Melissa Wilson-Sayres (ASU) and Dr. Ken Buetow (ASU).

This work is supported by the Multiple Myeloma Research Foundation.

Understanding response to Car t cell therapy using single cell RNa-seq in PATIENTS with GBM 

Glioblastoma is an aggressive brain cancer affecting roughly 10,000 individuals per year in the United States. Unfortunately, fewer than 5% of patients diagnosed with GBM will survive longer than five years. Recent advances in immunotherapy - particularly CAR T therapy - have shown promise for the treatment of GBM; yet, substantial variation in response to CAR T therapy exists - in GBM as well as other tumor types. The Banovich lab has formed a collaboration with Dr. Christine Brown (City of Hope) to deeply characterize CAR T cell product, peripheral blood, and tumor samples from Dr. Brown’s groundbreaking clinical trial using single cell RNA-seq and other omics technologies. This work will aid in our understanding of the molecular phenotypes associated with clinical response to CAR T cell therapy.