The Lankenau Institute for Medical Research
The faculty at LIMR focus their investigations on cancer, cardiovascular disease, and diabetes. Some individuals choose to sponsor a specific research project to support. Below are some of the current research projects that are being worked on at LIMR.
In collaboration with MIT, scientists in Dr. Janet Sawicki’s laboratory are developing a new therapy to safely and specifically destroy cancer cells through the utilization of nanotechnology to deliver engineered DNA molecules. These molecules are naturally processed by cancer cells and lead to their controlled destruction. Currently, this research focuses on the creation of new treatments for advanced prostate and ovarian cancers as well as breast and pancreatic cancers.
Solid tumors are widely treated through radiation and chemotherapy, however, within these tumors there are areas where glucose and oxygen are largely depleted i.e. in hypoxic conditions. It is in these areas that cancer cells are often resistant to treatment. LIMR scientists in Dr. Ira Ayene’s lab are developing a new approach to specifically destroy cancer cells in human solid tumors by using unique non-toxic (to normal tissue) thiol containing oxidants. Data from preliminary experiments demonstrate that these compounds act synergistically with chemotherapy or radiation.
In cancer patients, disruptions in the regulation of enzymes that modulate the immune response promote tumor progression by protecting cancer cells. LIMR scientists in Dr. George Prendergast’s group have identified a safe compound to increase the immune response mounted against tumors while chemotherapy is being delivered. An ongoing clinical trial using our compound is confirming that stimulation of the immune system could lead to a great improvement in long-term survival of cancer patients and encourage us to develop new therapies to treat illnesses that are promoted by a dysregulation of the immune response.
Antibody therapeutics represent one of the most promising class of human therapeutics, however, methods for obtaining these molecules have long been technically complex, labor intensive, expensive and often ineffective. LIMR scientist Dr. Scott Dessain and those in his early stage company, Immunome, Inc., which is incubating in our facility, have developed novel technologies and screening methods to address these issues. Together they are working towards putting in place a screening facility that will allow for the effective identification, isolation and ultimately production of native human antibodies to be directly used as therapeutics in cancer, autoimmune disorders and infectious diseases.
High-throughput screening (HTS) of chemical and biological compounds is used to validate newly discovered proteins as important targets for medicinal intervention. Once a biological target is validated as ‘drugable’, interest in licensure by pharmaceutical companies and availability of venture capital for commercialization of new medicines is markedly enhanced. Large compound libraries that are required for successful leads discovery are usually stored, organized and accessed inefficiently and in ways that ultimately degrade the quality of the chemicals compromising all future drug discovery campaigns. LIMR scientist, Dr. Mel Reichman and those in his early stage service company, LIMR Chemical Genomics Center (LCGC) have developed new technologies to address these issues and optimize high-throughput screening by putting in place a state of the art chemical storage and retrieval facility at LIMR. Such a facility was once reserved for large pharmaceutical groups only and will accelerate discoveries here and in academic laboratories within our region.
Esophageal cancer is increasingly common in the U.S. and lethal when not diagnosed in its earliest stage. The basic function of the esophagus is to act as a barrier to keep the foods we ingest inside the tube heading to the stomach. Developing cancer cells do not fulfill this task very well and create a “leaky” zone in the esophageal lining. Dr. Jim Mullin and his laboratory are developing a simple sugar drink test to determine the degree of “leakiness” that will let physicians know whether a patient with frequent heartburn is at particular risk for cancer of the esophagus. Interestingly, this group has also discovered that a commonly taken medication can induce a leak in the stomach lining that requires further investigation to determine if it posses a health hazard.
A significant subgroup of breast cancer patients diagnosed with small ductal carcinomas and who would be expected to be disease-free at 5 years after diagnosis will actually suffer a recurrence or succumb to their disease within that period. Drs. George Prendergast and Maggie Wallon are developing a test to use the protein TIMP-4 as a marker to identify, at a very early stage, the most aggressive form of invasive ductal breast carcinoma. This test will help physicians select the best treatments by predicting clinical outcomes in early stage breast cancer patients.
The heart muscle is damaged by a heart attack. LIMR investigator Mindy George-Weinstein who are experts in muscle cell biology are currently studying stem cells that have the potential to rebuild heart tissue after a heart attack. Using eggs from chickens, their research is discovering optimal ways to convert stem cells into healthy heart muscle cells. This should provide an opportunity for a practical application of stem cell therapy in the future. In an interesting off shoot of this work, these scientists, in collaboration with those at Jefferson Medical College have found that muscle stem cells when stimulated inappropriately may contribute to re-clouding of the lens that commonly occurs after cataract surgery.
A new therapy for the most common form of oral cancer, squamous cell carcinoma is being developed by LIMR scientists in Dr. Thomas O’Brien’s laboratory. The therapy involves administering two drugs that work together to starve tumors of polyamines that are essential for tumor growth. A joint program with the University of Pennsylvania School of Veterinary Medicine has been established to conduct clinical trials of the therapy in cats and dogs with oral cancer. The results of a recent small animal trial have been very encouraging: several objective tumor responses were observed and the average survival time was significantly extended. One subject is still alive almost a year after diagnosis, much longer than expected 4-6 weeks. While these trials have obvious value for owners of companion animals, they also will help in the design of forthcoming trials of the therapy in humans.
High blood pressure is an invisible killer with few symptoms but devastating consequences such as stroke and heart disease. LIMR investigators Dr. Robert Cox and his laboratory study how blood pressure is regulated and how cardiovascular muscle function is maintained. The promise of this research is to put the patient on the right medication for their condition to optimize their treatment while reducing side-effects.
LIMR scientists are collaborating with CureDM, Inc. an early stage company incubating in our facility to better understand the mechanism by which their new treatment for type 1 and type 2 diabetes works. Principal collaborator for LIMR is Dr. Lisa Laury-Kleintop whose expertise in determining how cells respond to external signals is being utilized to identify the receptor and pathway by which the CureDM therapy delivers its generative signal.