Our Research
We are dedicated to developing innovative treatments for patients with metastatic melanoma.
There have been remarkable advances in our treatment of melanoma over the last 5 years. Despite these successes, not all patients benefit equally from these treatments. Dr Haq and his lab attempts to understand why treatments that are remarkably effective in some patients, fail to work in others. In other instances, treatments may work only for a period of time, before they stop working—we ask, why? It is our hope that our understanding of these key questions will allow us to rapidly develop novel therapies for our patients.
Our research falls into two major categories:
1. Targeted therapies, such as BRAF inhibitors. We have demonstrated that BRAF inhibitors not only induce cytotoxic pathways in melanoma cells, but also induce pathways that paradoxically promote survival (for example, Haq et al, Cancer Cell (2013)). We are characterizing these “adaptive resistance” pathways at a deep molecular level, so we can develop combinatorial approaches to overcome this resistance. Our comprehensive surveys suggest that this form of resistance is ubiquitous in melanoma and in virtually all other cancer types. We are especially interested in the role of the mitochondrion and oxidative metabolism in resistance to targeted therapies.
2. Immunotherapies. We are developing new models to evaluate resistance to immunotherapy. Using these approaches, we have designed comprehensive screens to identify mechanisms of innate resistance to immunotherapies such as PD-1/PD-L1 inhibitors and CTLA-4 checkpoint inhibitors. Characterizing candidate resistance pathways at a molecular level will lead, it is hoped, to the development of strategies to improve these treatments using combinations of small molecules and immunotherapies.
3. Uveal melanoma. We are developing new strategies to target uveal melanoma. Please see our work here.
There have been remarkable advances in our treatment of melanoma over the last 5 years. Despite these successes, not all patients benefit equally from these treatments. Dr Haq and his lab attempts to understand why treatments that are remarkably effective in some patients, fail to work in others. In other instances, treatments may work only for a period of time, before they stop working—we ask, why? It is our hope that our understanding of these key questions will allow us to rapidly develop novel therapies for our patients.
Our research falls into two major categories:
1. Targeted therapies, such as BRAF inhibitors. We have demonstrated that BRAF inhibitors not only induce cytotoxic pathways in melanoma cells, but also induce pathways that paradoxically promote survival (for example, Haq et al, Cancer Cell (2013)). We are characterizing these “adaptive resistance” pathways at a deep molecular level, so we can develop combinatorial approaches to overcome this resistance. Our comprehensive surveys suggest that this form of resistance is ubiquitous in melanoma and in virtually all other cancer types. We are especially interested in the role of the mitochondrion and oxidative metabolism in resistance to targeted therapies.
2. Immunotherapies. We are developing new models to evaluate resistance to immunotherapy. Using these approaches, we have designed comprehensive screens to identify mechanisms of innate resistance to immunotherapies such as PD-1/PD-L1 inhibitors and CTLA-4 checkpoint inhibitors. Characterizing candidate resistance pathways at a molecular level will lead, it is hoped, to the development of strategies to improve these treatments using combinations of small molecules and immunotherapies.
3. Uveal melanoma. We are developing new strategies to target uveal melanoma. Please see our work here.