The main focus of LIMR continues to be in cancer research. The field is unusually broad, reaching at basic levels into virtually all aspects of biology and biomedical science. Thus, cancer research inherently spans biological science from basic to clinical levels.

LIMR has historical strengths in cancer research that date from its origins in 1927 (see Our History). LIMR researchers have built a national reputation in chemical carcinogenesis. They also have unique strengths in cancer genetics, in particular, moving to study a newly emerging group of cancer susceptibility genes that are called modifier genes.

Dr. O’Brien and Dr. Gilmour study genetic principles of skin carcinogenesis that are fundamental to solid tumors (carcinomas), which represent the major deadly forms of human cancer. Dr. O’Brien’s laboratory has pioneered research at LIMR into modifier genes that dictate susceptibilities to cancer and their treatment. His recent work in this area has focused in part on prostate cancer in collaboration with Dr. Michael Hagg in Urology and and Dr. Albert DeNittis in Radiation Oncology at Lankenau Hospital. In addition to his genetic studies, Dr. O’Brien is also conducting pharmacological studies aimed at correcting the consequences of the major genetic defect he has examined (overexpression of the enzyme ornithine decarboxylase). In her studies, Dr. Gilmour has focused her work in carcinogenesis on the contributions of the tumor stroma – the parts of the tumor that do not include the tumor cells themselves. Modifier genes and the tumor stroma are emerging as the predominant forces driving cancer progression, therefore, they have gained significant attention at LIMR with regard to therapeutic exploitation.

Dr. Mandik-Nayak is an immunologist who studies mechanisms of inflammation and immune tolerance in arthritis that are relevant to cancer and cardiovascular disease. Her investigations focus on T and B cell dysfunction in transgenic mouse models of rheumatoid arthritis. The themes in Dr. Mandik-Nayak's research are highly relevant to chronic inflammatory and immune problems that occur in a variety of diseases, including atherosclerosis and cancer.

Dr. Mullin studies cancer at the level of tissue physiology, specifically, in the breakdown of barrier function of epithelial tissues in the gastrointestinal tract. His work has focused mainly on colon and other gastrointestinal cancers, using rodent models and human tissues for study. Dr. Mullin’s research has recently led to a surprisingly simple idea to screen for esophageal cancer, one of the deadliest and fastest growing cancers in the U.S. Clinical development of this screening method, performed in collaboration with Dr. James Thornton in Gastroenterology at Lankenau Hospital. This translational project represents a major effort of Dr. Mullin’s laboratory.

Dr. Prendergast and Dr. Muller work on cancer suppression genes that modify molecular trafficking processes and other processes in cells. An important direction emerging from their work relates to immune control of cancer. Dr. Prendergast’s investigations have focused on cancer cell suicide processes and, more recently, on an immune evasion process mediated by the enzyme indoleamine 2,3-dioxygenase (IDO) that has emerged from collaborative studies with Dr. Muller. Their work uses transgenic mouse models of cancers of the breast, skin, intestine, and lung. Using his expertise in cancer pharmacology and mouse models of cancer, Dr. Muller has translated the work on IDO into a novel drug strategy that “supercharges” the activity of cancer chemotherapy in preclinical settings. This new technology has been patented and licensed to a pharmaceutical company for clinical development.

Dr. Sawicki works on nanotechnology-based gene therapies to treat advanced prostate cancer. She is an expert in the development, analysis, and imaging of mouse models of prostate cancer – tools which are critical for preclinical development of novel therapeutic principles. Dr. Sawicki has coupled nanotechnology to gene therapy to pioneer a more specific and effective modalities for disease treatment. In other work, Dr. Sawicki is studying prostate stem cells to gain new understanding about the basic biology of the prostate.

Dr. Soler is a board-certified clinical anatomic pathologist who also has specialized expertise in murine pathology. His expertise is extremely valuable to the many faculty who collaborate with Dr. Soler in their broad use of murine models of disease (e.g. in basic genetic studies and in preclinical analysis of new therapeutic agents). The contributions of Dr. Soler are very imporant to LIMR and a major asset to its overall excellence in preclinical disease models.

Dr. Stamato and Dr. Ayene study the fundamental processes of gene repair in cancer. The goal of their work is to learn how to enhance the efficacy and specificity of radiotherapy for cancer. Their investigations focus on mechanisms of non-homologous end joining (NHEJ) by the Ku proteins in DNA. A major focus of Dr. Stamato's present work is the characterization of a novel DNA end-binding activity in cells. Dr. Ayene specializes in understanding how hypoxic conditions present in tumors can cause resistance to radiotherapy. A major focus of his present work is a novel pathway for reversing radioresistance of hypoxic tumor cells.

Dr. Wallon is interested in tumor-stroma interactions that cause breast tumor invasion. Her work has focused on matrix metalloproteinase systems that control invasion of cancer cells. Using breast cancer models and human breast cancer tissues, she has pursued lines of investigation leading toward (1) a prognostic test that may distinguish poorly and highly invasive tumors at early stages of development (Stage 0/1-2), and (2) a biologic strategy to block the enzyme system as a method to staunch the invasive capabilities of more advanced cancers.

• Iramoudi (Ira) Ayene, PhD
• Susan Gilmour, PhD
• Laura Mandik-Nayak, PhD
• Alexander J. Muller, PhD
• James M. Mullin, PhD
• Thomas G. O'Brien, PhD
• George C. Prendergast, PhD
• Janet A. Sawicki, PhD
• Thomas D. Stamato, PhD
• U. Margaretha Wallon, PhD