Miami, Florida 33136
Tel: (305) 585-6303
Fax: (305) 326-9363
Ongoing Research
Our investigators are involved in multitude of projects. Diversity of population and ample amount of clinical samples provides a unique opportunity for clinical and translational research in our campus and nationwide as is demonstrated by our NIH funded tissue banks. We are also technology innovators in laboratory practice in areas like flowcytometry and tissue processing. The following is a summary of current research themes in our department.
Astrocyte Biology
Laboratory is investigating the function of astrocytes and their role in neurologic disease. A major focus involves mechanisms of cell swelling (cytotoxic brain edema). In particular, the role of oxidative/nitrosative stress, mitochondrial dysfunction (the permeability transition), transcription factors and signal transduction mechanisms, and how these factors interact to bring about a disturbance in plasma membrane ion transporters, ion exchangers, as well as in the water channel, aquaporin, that ultimately result in the inability of the astrocyte to adequately regulate its cell volume. Disorders being investigated relative to disrupted cell volume regulation include hepatic encephalopathy, trauma and ischemia. Other areas under investigation include the involvement of astrocytes in the mechanism of neurodegenerative diseases (Parkinson's, Alzheimer's), manganese and copper neurotoxicities, and trauma-induced neuronal cell death (in culture). We also have a large bank of human spinal cord injury specimens in which we examine basic mechanisms of tissue injury. Methodologies used in the lab include cell culture, in vivo models of disease, cell imaging, standard molecular biology techniques, gene up- down-regulation (via viral transfection, siRNA), neurotransmitter binding and transport, and a battery of morphological techniques.
Traumatic Brain Injury
Research is focused on the molecular mechanisms of traumatic brain injury, with a particular emphasis on the role of purinergic signaling in the formation of reactive astrocytes. These cells produce a variety of molecules, some which impede, and others which promote, axonal regeneration. An understanding of the signal transduction mechanisms that regulate the expression of these molecules may offer an opportunity to enhance the beneficial, axonal growth-promoting features of reactive astrocytes while attenuating their harmful, growth-inhibiting properties. Thus, important advances in the understanding the mechanisms leading to astrogliosis may provide new therapeutic approaches to restore deficits in motor skills and cognitive functions caused by brain injury.
Analytical Cytometry
High Resolution Flow Cytometers: Laboratory has been involved in development of a high resolution flow analyzer in collaboration with NPE Systems, Inc of Pembroke Pines, Fl. Our initial efforts supported by grants from the Florida Division of American Cancer Society and National Institutes of Health led to the development and testing of a flow cytometer for the NASA. This high resolution flow analyzer which can simultaneously measure cell volume and fluorescence of cells is now marketed by Beckman Coulter as Quanta SC Flow analyzer.
Dedicated Flow Cytometer for Detection of Tumor Cells in Body Fluids: Laboratory is funded at present by the Florida Department of Health for modifying the NPE flow analyzer for detection of tumor cells in body cavity fluids such as pleural and peritoneal fluids.
Marker Expression in Cells from Body Cavity Fluids: This project focuses on use of high resolution flow cytometry for monitoring the expression of diagnostic markers in tumor cells from body cavity fluids. We have developed rapid flow immunocytochemical methods for identification of markers which identify a cell as being malignant and also suggest their probable origin. These findings were recently reported and show that flow cytometry in combination with conventional cytology can be used to detect tumor cells in body cavity fluids. This work was earlier supported by a grant from the National Cancer Institute and currently is funded from a grant from the Women’s Cancer Association.
Marker Expression in Breast Tumor Cells: Laboratory has developed rapid methods for flow cytometric analysis of nuclear marker expression in breast and prostate tumors. This work is especially important for quantitative estimation of markers such as estrogen and progesterone receptors on tumor cells. This work supported by the Florida State Department of Health is focused on rapid analysis of other diagnostic markers in breast cancer.
Effect of Anti-tumor peptides in Breast and Prostate Cancer
Breast cancer research on the evaluation of the activity of various anti-tumor peptides, in Estrogen Independent Breast Cancer cell Lines and in vitro in specimens. Investigation will be expanded in vivo in various breast cancer lines of the effects of GHRH antagonists and other analogs like Cetrorelix and Bombesin antagonists RC-3095 or RC-3940-II. Investigation of the effects on levels of IGF-I, IGF-II, EGF (and HER 2, 3, 4), FGF and VEGF, hypothalamic peptides LHFH somatostatin, bombesin/GRP, and their receptors. A variety of effects on oncogenes c-fos, c-ras, c-jun PKC is investigated too.
Prostate cancer and BPH research is focused on GHRH antagonist in androgen-dependent and androgen-independent prostate cancer and BPH. Investigation of why androgen dependent models require androgen suppression by LHRH agonists, antagonists or flutamide for a response to GHRH antagonists while androgen independent models such as PC-3, DU-145 do not. Effects of therapy with Cetrorelix on the levels of various growth factors and their receptors in patients with BPH would also be investigated. Also being investigated are the effects of therapy with Cetrorelix on vascularity of hypertrophied prostate tissue in patients with BPH scheduled to undergo surgery.
Clinical Chemistry and Forensic Toxicology Research
The Clinical Chemistry Section of Jackson Memorial Hospital’s Core Laboratory serves a large and varied patient population. Thus, it has clinical material that makes it possible to participate in numerous studies involving evaluating new methods and instrumentation. A related activity of the Section is the study of various analytical methods to determine whether or not they have the accuracy in terms of precision and trueness to meet medical needs.
Patterns of drug abuse in a community change with time, and there have been several recent advances in using alternative samples, i.e., saliva, and hair. Thus, the Forensic Toxicology Laboratory of University of Miami must constantly change its approach to testing and its analytical methods of testing. The Laboratory has an active program of developing new analytical techniques by GC/MS and LC/MS/MS. It also interacts with other departments and investigators in developing drug and toxin assays for various research projects.
Cooperative Breast Cancer Tissue Resource (CBCTR)
The Cooperative Breast Cancer Tissue Resource (CBCTR) was developed, starting in 1993, in response to a cooperative agreement between the National Cancer Institute and four sites in the United States to provide primary breast cancer tissue to the biomedical research community for the study of clinical markers of tumor prognosis and the evaluation of promising diagnostic tests based on these markers. The four sites comprising the CBCTR are University of Miami/Jackson Memorial Hospital in Miami, FL., Fox Chase Cancer Center in Philadelphia, Pa., Washington University in St. Louis, Mo., and Kaiser Permanente in Portland Oregon. Between the four sites there are over 9000 breast cancer cases with their associated clinical/outcome and pathological data. The distribution of cases in the Resource closely parallels National Cancer SEER data.
All the material is formalin fixed paraffin embedded and spans three decades of materials. The material provided is in the form of Full Tissue Sections or Tissue Microarrays that incorporate specimens from hundreds of cases on one or two slides. Investigators can obtain additional information or apply for material at http://cbctr.nci.nih.gov/
NICHD Brain and Tissue Bank
The National Institute of Child Health and Development (NICHD) Brain and Tissue Bank (BTB) at the University of Miami were established in 1993. Its mission is to provide human material for investigators studying normal brain development and diseases that alter the development or maturation of the nervous system.
The NICHD & BTB has been highly successful in meeting this challenge. As of May, 2006, it has accrued over 900 autopsies, 710 surgical biopsies and 1000 cell culture lines. All cases are given a unique identifying number and patient identifiers are removed from the records. The NICHD & BTB uses institutional review board informed consents to obtain permission to donate tissues and organs and maintain appropriate HIPPA compliance. Research tissue from the brain and tissue bank has been distributed to over 150 investigators, most of whom have NIH research grants.
Diseases of interest to the Brain Bank include autism, chromosomal abnormalities, congenital brain malformations, musculo-skeletal disorders such as spinomuscular atrophy and muscular dystrophy; and acquired diseases such as perinatal asphyxia and trauma. Most of the cases are from infants and children with such disorders. In addition, the Bank collects and distributes normal tissue as controls for studies relating to normal brain development and maturation.
Research Molecular Pathology and Tissue Profiling Laboratory
The lack of standards in tissue preparation, combined with the physical and chemical nature of conventional processing make formalin fixed paraffin embedded tissue of limited value for molecular research. We have recently developed a novel and rapid method of processing human tissues for histopathological evaluation. In contrast to conventional overnight tissue processing methods, Rapid Tissue Processing technology (RTP) allows for histopathological evaluation of tumors within hours of collection. When RTP is combined with a newly developed molecular-friendly fixative (UMFIX- Universal Molecular FIXative), cellular macromolecules such as high molecular weight RNA DNA and proteins are preserved in the paraffin embedded tissue. When compared to conventional formalin fixation and routine overnight processing methods, the new fixation and processing technology offers the unique opportunity to combine excellent histopathology with the preservation of bimolecular (e.g., DNA, RNA and proteins) in archival paraffin blocks. Therefore clinical material procured by this system can be reliably used both as platform for biomarker discovery and clinical molecular diagnostics. This is a unique well-published system that has been an outstanding performer in intellectual property arena for University of Miami.
Biomarker discovery and validation-Using our novel technology for preserving macromolecules in clinical tissue samples our group is applying genomics and proteomics methods o identify primarily tissue/disease specific biomarkers. Current projects include validation of epigenomics biomarkers in thyroid cancer. We are also identifying biomarkers for estrogen receptor negative/basal type breast cancer using high-throughput screening methods and using quantitative mass spectrometry for their validation.
