Request for Funding

Medical Student Research Fellowship for Summer 2004

Mentor: Howard Heller, M.D.
Department: IM
Room number: CS6.104
Mail Code: 8885
Phone number: 82117
E-mail: Howard.Heller@utsouthwestern.edu
Project title: You will be given one long-term project and at least one short-term project.

Human subjects IRB approved project number (where applicable): 0899 340

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

Project Type Patient-oriented clinical research

Brief Description of Project:

I. The Role of the Bone in Severe Absorptive Hypercalciuria:
Absorptive hypercalciuria (AH), the most common cause of nephrolithiasis, results from primary enhancement of intestinal calcium absorption. Counterintuitively, patients with severe forms of the disease also have low bone mass and negative calcium balance. Physiologic explanation for the contradictory bone loss in the setting of excessive intestinal calcium absorption has not been fully delineated.
The goal of this project is to better elucidate the pathophysiologic mechanisms for bone loss and hypercalciuria in severe AH to allow formulation of more rational treatment modalities. Each patient with severe AH will be compared to matched normal volunteers, for:
A) Bone biopsy and bone turnover markers to evaluate whether the primary problem is increased bone resorption, decreased bone formation or impaired bone mineralization.
B) Response of urinary calcium to an agent that blocks bone resorption (we expect the patients with excessive bone resorption to demonstrate a more exuberant decrement in urinary calcium than the normal volunteers)
II. Does Melatonin Reduce Urinary Calcium:
Melatonin, an over-the-counter supplement, is known to have some effects on mineral metabolism. My interest in studying this drug is based on my experience with a patient in clinic. His urinary calcium suddenly fell > 50% after he started the drug on his own. When he stopped melatonin, urinary calcium rose to baseline; urinary calcium fell again when he restarted the drug. I have just submitted a pilot protocol to confirm that melatonin lowers urinary calcium and to investigate the physiologic mechanism of this action, the effect on other stone risk factors, and the elucidation of the duration of action of melatonin and the optimal dose to lower urinary calcium.

III. Unraveling the Genetic Causes of Kidney stones
This research bridges the bedside to the bench, and hopefully back again. You would be involved in arranging family gatherings at which we would perform clinical studies and collection of blood for gene analysis. We have already found a gene that is associated with hypercalciuria and low bone mineral density by such studies
IV. Mock Protocol in Clinical Research
You will choose a scientific question of interest to you, and develop a basic plan to study it.
V. Publishable Report
If you desire, you will be given a choice of several interesting diseases to write-up potentially publishable case reports or case series.

Previous Research Activities or Publications with Medical Students:

I have mentored two summer students. Mark Doerner completed most of a project comparing the risk of stone formation between two diets. He gave an oral presentation of his work at the Student Research Symposium, and he was second author on the paper (J Urol 2003; 169:470-474). Laura Greer completed much of a project comparing calcium absorption between 2 commercial supplements and placebo. She was the 2nd author in the resulting publication (J Clin Pharmacol 2000, 40 (11): 1237-44).

You will be exposed to all aspects of clinical and research in mineral metabolism including planning a study, recruiting subjects, collecting and analyzing data, and submitting a manuscript for publication. In addition, you will rotate in our clinics and will be exposed to clinical mineral metabolism (diseases we follow include osteoporosis, osteomalacia, osteogenesis imperfecta, Paget's disease of the bone, kidney stones, and disorders of calcium, phosphorus and magnesium).

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