Fighting Cancer and Disease, One Lymph Node at a Time

Timothy P. Padera, MEMP PhD, ‘03, Associate Professor of Radiation Oncology at Massachusetts General Hospital/Harvard Medical School

Tim Padera works to fight cancer and disease by focusing his research on a far-reaching system of the body—the lymphatic system. As part of the Edwin L. Steele Laboratories for Tumor Biology at Massachusetts General Hospital, the Padera Laboratory uses novel intravital microscopy tools to examine how the lymphatic system drives the progression of cancer through metastatic spread as well as impairment in anti-tumor immune function. In addition, the Padera Lab studies the molecular control of lymphatic pumping and how pumping regulates antigen transport and the initiation of an immune response. These processes are dysfunctional in a variety of disease states including lymphedema and bacterial infections.

Although Tim’s research program is based in the lab, his clinical experiences as an HST MEMP student helped him define what is needed to have an impact on patient care. Patient care is ultimately what drives the work of the Padera Lab.

Like many of his classmates, Tim was first drawn to HST’s MEMP PhD program by the combination of rigorous engineering education with medical school course work and clinical experiences. Tim recalls that “the time I spent meeting and working with the medical students and building those relationships helped me understand what practicing medicine entailed, including how data is really collected and how decisions are really made based on that data. That was eye opening and pulled back the curtain on a lot of the practice of medicine that I’d never seen before. With that insight, it helped frame the environment in which clinicians need to care for their patients.”

Keeping this clinical perspective central in his mind informed Tim’s studies then and continues to weave its way into his current projects. He consistently focuses on what the outcomes of those projects should be in order to have an impact on the practice of clinical medicine.

Tim came to HST with a chemical engineering background. The world made sense to him from the chemical engineering perspective. “It’s a lot of mass balances and flows, transport of molecules and heat. All of that made sense as I started looking for problems in how the normal body operates and how those type processes of fluid balance and molecular transport are changed in disease processes.” As a MEMP student, Tim developed the skills needed to identify unsolved medical problems.

“I explored a variety of projects related to that in search of my thesis project. There were a lot of drug delivery projects as well as work on both tissue engineering and bioreactor design type projects that could lead to the creation of artificial organs . . .” to replace a non-functioning organ and carryout the necessary tasks in the body.

Tim said, “when I weighed all the options, I found I was drawn to the cancer projects because it is a disease where rules of normal physiology seem to get broken consistently and trying to unravel and potentially exploit that to develop better ways to treat cancer patients; I thought—this is something that I’ll be excited about on day one and also at the end of my thesis. I think I made a good choice as I’m still doing cancer research now.”

As a MEMP student, Tim worked in the laboratory of Dr. Rakesh K. Jain at MGH studying the processes of lymphatic metastasis. He is currently working to understand how cancer interacts with the lymphatic system.

In addition to studying the behavior of cancer in the lymphatic system, Tim’s research program also looks at other lymphatic diseases, such as lymphedema. “The lymphatic system helps organize the immune system and also pulls fluid out of tissues. Without the lymphatic system you get fluid retention, which is a process called lymphedema. It occurs in patients either genetically or from some kind of surgery or trauma. There’s currently no effective treatment for lymphedema.”

This lymphatic system dysfunction plays a role in many diseases and contributes to pathogenesis or inflammation (which can effect many diseases processes) as well as obesity, which also stunts lymphatic function and may contribute to the retention of adipose tissue.

One area that his lab has made progress in is understanding bacterial infection and how it is cleared by the body. . Certain bacteria try to preserve the niche that they’ve created in an affected tissue by inhibiting lymphatic function and preventing the immune system from really kicking in. In all of these diseases where the lymphatic system plays an integral role, one of the key goals that Tim’s group hopes to achieve is to restore the body’s immune function as a means of fighting illness.

By understanding the molecular control of these processes, the first drugs targeting lymphatic function can be developed to help in the treatment of lymphatic related disorders. The ability to identify unsolved medical problems that Tim gained in HST has helped shape the types of research questions the Padera Lab tackles. “We strive to identify unmet needs in the treatment of metastatic cancer and lymphatic related diseases. We hope to one day translate the results of our research to improve patient care.”

Dr. Padera has been nationally recognized for his creative and novel scientific program in lymphatic metastasis by an NIH Director’s New Innovator Award.