irAEs

Immunotherapy is a novel cancer therapeutic modality.  While promising, it can induce sometimes severe side effects called immune-related adverse events (irAEs).  Common treatment for irAEs can impact effectiveness of the cancer therapy.

Understanding the causes of these irAEs can enable targeted treatment that improves patient quality of life and does not impact the therapeutic effectiveness of immunotherapy.

The Kulkarni lab is focused on studying cutaneous and mucosal irAEs using patient tissue and murine models.

Collected patient tissue is analyzed with scRNA-seq and immunohistochemistry analysis to understand the cell populations present that are contributing to the irAE.

Mouse models replicate a skin rash irAE using a dermatological irritant or genetically-induced immune reaction at the skin.  These models provide a platform to test the effectiveness of different treatments with and without tumor and immunotherapy.

Organoids

The Kulkarni lab uses human patient or mouse tissue to grow and treat intact tissue as organoids in culture.  Using these cultivated tissues we can directly test the effects of different drugs on immune cell composition human skin or mouse tissues. 

We are actively expanding our capabilities in this project through collaborations with investigators at the Knight Biofabrication hub.  Currently we are focused on building and validating an organoid melanoma and skin protocol to understand the effects common immunotherapy drugs have on cancer and normal skin.

CD74/MIF

Macrophage migratory inhibiting factor (MIF) is often overexpressed in cancer, including in melanoma. Higher MIF expression is correlated with worse outcomes in cancer.  Inhibition of MIF signaling with its receptor, CD74, is an exciting new pathway to investigate for melanoma treatments.  This pathway is also independent of other common cancer therapeutic targets, creating the potential to treat patients who fail or cannot take other cancer therapies.

We are currently collaboratively developing a novel peptide drug that blocks the MIF/CD74 axis and testing use of this drug to treat melanoma using several relevant mouse models.  The lab is further investigating for the specific pathways this therapy may be utiilzing to prevent tumor growth.