 |
about | Maps & Directions | contact | admissions | faculty | alumni & development | library | Tech Support Center | dean's office | Policies & Procedures |
 Site Map
|
|
about | Maps & Directions | contact | admissions | faculty | alumni & development | library | Tech Support Center | dean's office | Policies & Procedures |
 |
 |
 |
FAculty directory
Associate Professor, Biochemistry Associate Professor, Fels Institute for Cancer Research and Molecular Biology Director, Proteomics Core Telephone: 215-707-9228 Email: salim.merali@temple.edu
Fels Institute of Cancer Research And Molecular BiologyDepartment of Biochemistry
Our laboratory focuses on identifying novel biochemical approaches to the treatment/diagnosis of Pneumocystis pneumonia (PCP) and cancer. PCP is associated with AIDS, malnourished infants and immunosuppressive drugs used for cancer, organ transplant and rheumatic diseases. Although we have explored many areas, including metabolism of folates, polyamines, and iron as well as culture, recently our emphasis has been on the metabolism of S-adenosylmethionine (AdoMet). An intersection between Pneumocystis and cancer research occurred as a result of a study of the relationship between plasma AdoMet and Pneumocystis pneumonia (PCP). We found PCP causes a drastic reduction in plasma AdoMet of experimental animals and became involved in a clinical investigation to determine whether this was also true in patients. We also found that AdoMet depletion does occur in human PCP; it is dramatic enough possibly to become the basis of a technique for minimally invasive diagnosis of this disease and for monitoring the response to therapy. In the course of the study we also discovered that cancer causes a remarkable increase in plasma AdoMet.
AdoMet is a critical biochemical intermediate serving both as the methyl donor for a myriad of biochemical events and as a precursor to the higher polyamines. Methylation is associated with control of protein and DNA function and polyamines are known to help condense and stabilize DNA and RNA. Thus defects in either methylation or polyamine metabolism can interfere with normal control of cell function and proliferation. The fact that AdoMet is highly elevated in the plasma of cancer patients perhaps reflects the lack of control of function and proliferation of cancerous tissue. One of our ongoing research projects is testing the hypothesis that plasma AdoMet can be used as a serological marker for the presence of cancer. We are analyzing plasma AdoMet of patients with various malignancies including those with GI, lung and breast cancers. The data we have already collected and other studies show that disturbed AdoMet metabolism is characteristic of malignancies; however, the mechanism behind the elevation of plasma AdoMet is unknown. We found an increase in the activity of AdoMet synthesizing enzyme in tumor tissue is involved but is not likely to be the whole story.
Biochemical and Molecular Properties of Pneumocystisand Cancer as Basis for Diagnosis and ChemotherapyAlthough we are involved in the investigation of AdoMet metabolism and cancer, our research in Pneumocystis continues. We have been able to find metabolic differences between host and Pneumocystis and now host and cancer cells. The expectation is that such differences are ripe areas for rational development of drugs as well as for developing an understanding of the pathology of these diseases. As our research has evolved, it became clear the tools and techniques we had developed earlier are now included with other tools and techniques to create a new fields of metabolomics and proteomics. We have turned fully in this new direction and have been able to equip the laboratory with capillary electrophoresis, MALDI TOF/TOF mass spectroscopy, nano liquid chromatography ion trap mass spectroscopy/mass spectroscopy, Ettan IPG phor system for two dimension electrophoresis, high pressure liquid chromatography, etc. We are applying those tools to create a better understanding of the role of AdoMet in Pneumocystis and cancer cells with the expectation that the data will lead to improved ways of treating/diagnosing PCP and cancer.
|
|
Salim Merali , PhD 