Medical Student Research Fellowship for Summer 2006

Mentor: William M. Lee, MD
Department: Internal Medicine/Division of Digestive and Liver Diseases
Room number: L5.210
Mail Code: 8887
Phone number: 214 648 3323
E-mail: William.lee@utsouthwestern.edu

Project #1 title: Molecular epidemiology of fulminant hepatitis A

Human subjects IRB approved project number (where applicable): (re-approval pending)

Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): Patient based

Brief Description of Project #1: The Acute Liver Failure Study Group is an NIDDK-funded multi-center study based at UT Southwestern. Twenty-three sites have contributed detailed clinical and laboratory data as well as bio-samples to the database and repository for ancillary studies of this rare orphan disease. One such study is underway with the aim of determining whether there are unique molecular markers in patients with hepatitis A that develop acute liver failure. Sera from 26 patients with acute liver failure due to hepatitis A from the ALFSG bank have already been sent to CDC Division of Molecular Virology lab for study. These samples have been pcr'ed and sequenced to identify unique sequences compared with non-fulminant cases. Whether or not unique sequences are identified, there will be specific findings that may relate to the clinical features of the cases. For example, specific genotypes of hepatitis A are associated with certain risk factors such as food-borne exposure vs. men having sex with men. The applicant will be in charge of analyzing and integrating the data from the case report forms with the data from CDC to write up the results of the study.

Project #2 title:: Do phosphatonins produce the very low phosphate levels observed in acute liver failure?

Human subjects IRB approved project number (where applicable): (re-approval pending)

Animal subjects IRB approved project number (where applicable): N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): Patient based

Brief Description of Project #2: The Acute Liver Failure Study Group is an NIDDK-funded multi-center study based at UT Southwestern. Twenty-three sites have contributed detailed clinical and laboratory data as well as bio-samples to the database and repository for ancillary studies of this rare orphan disease. Phosphate levels in acute liver failure are almost invariably low on admission to hospital. Paradoxically, high phosphate levels are also observed and have been associated with a poor outcome, probably due to concomitant renal failure. The mechanism for the low phosphate levels has not been elucidated, but is also observed following hepatic resections. Poor oral intake and increased uptake/redistribution in cells has been postulated in the setting of hepatocyte regeneration. Recently, the discovery of phosphatonins, plasma mediators of phosphaturia, has led to reconsideration of these issues. Profound phosphaturia has been observed after hepatic resection but measurement of phosphatonin levels have not been performed. An ancillary study proposal has been submitted to the ALFSG to perform a pilot study, measuring the most studied phosphatonin, serum fibroblast growth factor (FGF-23) in patients with various etiologies and varying levels of PO4 using an ELISA assay. We strongly suspect that FGF-23 levels will be found to be very elevated in this condition and that they will correlate inversely with serum PO4 levels. This study should provide an initial insight that might lead to further elaboration of the mechanisms underlying the low PO4 levels in this very ill group of patients.

Previous Research Activities or Publications with Medical Students:

Eric Suhler, class of 1998, won US Student Medical Association Prize (national competition) in the Basic Research Category, Galveston Texas, and Best Poster Award at Texas Medical Association, Austin Texas. This work was subsequently published:
Suhler E, Lin W, Yin H, Lee WM. Decreased plasma gelsolin levels in acute liver failure, myocardial infarction, septic shock and myonecrosis. Crit Care Med 25:594-8,1997.

Dai Park class of 2006, won one of four Poster Awards at UT Southwestern, January 2004. Title: Survival Rates of Chronic Hepatitis C Patients in a US University Referral Practice.

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