Uma N. Sundram, MD, PhD

Research/Lab website:   Department of Pathology

My research program is primarily centered on the exploration of mechanisms driving hematopoietic disorders in the skin. Compared to hematopoietic disorders (lymphomas, leukemias, and mast cell disease) that involve other organs in the body, such as the lymph node, bone marrow, and spleen, the counterparts of these diseases in the skin have a different clinical presentation, course, and outcome. For example, patients with the most common lymphoma that starts in the skin, mycosis fungoides, can have a long and fruitful life, if the disease is limited to the skin and does not involve other organs in the body. For this reason, clinicians usually treat these patients with more conservative therapies (such as topical steroids) to control the disease, rather than with systemic chemotherapy, as in the case of their systemic counterparts. The most common type of mast cell disease of the skin, urticaria pigmentosa, occurs frequently in children, and can regress before puberty. On the other hand, adult patients with mast cell disease that involve organs other than skin can have a more aggressive clinical course, with a subset of these patients dying from their disease. Although the characteristics of the genes and proteins that cause these diseases are currently being studied, a key discovery would lie in our ability to distinguish patients who are going to do well (because their disease will be limited to the skin) from patients who may not do as well. The importance of this distinction would be in the therapeutic approach: patients with more aggressive disease would get more aggressive therapy. Unfortunately, cutaneous lymphomas are notoriously difficult to diagnose accurately, as they can look very much like reactive processes under the microscope. Similarly, although it is relatively straightforward to render the diagnosis of mast cell disease in the skin, distinguishing mast cell disease that will spontaneously regress from those that will have a more aggressive clinical course can also be challenging.

The aim of my research group is to explore the genetic and protein expression patterns in these diseases when they are limited to the skin, and when they involve organs outside the skin, and to understand the differences between these two scenarios. This may aid greatly in diagnosis if there were, for example, proteins expressed in cutaneous mast cell disorders that were not present in mast cell diseases in other organs. It can also help therapy, if we were able to find specific genetic changes in clinically aggressive mycosis fungoides, which were different from mycosis fungoides limited to the skin. These genetic changes could then be used as a marker for patient response to different kinds of chemotherapeutic drugs. It is possible that drugs could be engineered to specifically interact with modified proteins associated with these genetic changes as well.