Dr. Hingtgen's Neurology Web Page
E-Mail:  chingtge@iupui.edu
 

    My current research involves exploring the mechanisms behind benign tumor formation in Neurofibromatosis Type I (NF1).  Neurofibromatosis Type I is one of the most common genetic illnesses.  It is an autosomal dominant disease characterized by the formation of multiple benign and malignant tumors throughout childhood and adulthood.  This disease is extremely disfiguring and disabling and can be deadly.  Neurofibromatosis Type I is caused by a mutation of the gene, on chromosome 17, that produces the protein neurofibromin.  Neurofibromin is a protein that serves as a GTPase activating protein (GAP) for p21^ras (Ras).  Neurofibromin converts Ras from its active GTP binding form into an inactive GDP binding form.  This pathway, with Ras as effector, is stimulated by many growth factors.  Its down stream effectors include the mitogen activating protein kinase (MAP kinase) pathway.  These transduction cascades are important in cell survival, growth and proliferation in many cells types.  The tumor formation seen in NF1 may be a result of dysregulation of this critical pathway secondary to the loss of neurofibromin production.  The most common tumors seen in patients with NF1 are benign cutaneous neurofibromas.  Schwann cells and primary sensory neurons are prominent cells in these tumors. 

My laboratory uses mice with mutation of the NF1 gene (Nf1) as a model.  Cells from these mice are grown in culture and abnormalities of Schwann cell and sensory neuron response to growth factors are examined.  The growth factor transduction cascades are examined biochemically and cell proliferation and survival are monitored.  The excitability of sensory neurons from mice with mutation of Nf1 is also being examined, using neuropeptide release as an endpoint.  These studies may help to explain the pain and abnormal sensory symptoms that patients with NF1 experience.

Publications:

Hingtgen CM, Nicol GD (1994) Carba prostacyclin enhances the capsaicin-induced cobalt loading of rat sensory neurons grown in culture.  Neurosci. Lett. 173:99-102.

Hingtgen CM, Vasko MR (1994) Prostacyclin enhances the evoked-release of substance P and calcitonin gene-releated peptide from rat sensory neurons.  Brain Res. 655:51-60.

Hingtgen CM, Vasko MR (1994) The phosphatase inhibitor, okadaic acid, increases peptide release from rat sensory neurons in culture.  Neurosci. Lett. 178:135-138.

Hingtgen CM, Waite KW, Vasko MR (1995) Prostaglandins facilitate peptide release from rat sensory neurons by activating the adenosine 3',5'-cyclic adenosine monophosphate transduction cascade. J. Neuroscience. 15:5411-5419.

Liu Y,  Jones M, Hingtgen CM, Bu G, Larabee N, Moir R, Tanzi R, Moir RD, Nath A, He JJ (2000) Uptake of HIV-1tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands.  Nature Medicine.  6:1380-1387.

 Hingtgen CM, Siemers E (1998) The treatment of Parkinson’s disease – current concepts and rationale. Comp. Ther. 24:560-566.

Hingtgen CM (1999) The painful perils of a pair of pianists: the chronic pain of Clara Schumann and Sergei Rachmaninov. Sem. in Neurol. 19(supp. 1):29-34.

Hingtgen CM (1999) The tragedy of Sergei Prokofiev.  Sem. in Neurol. 19(supp. 1):59-61.

Williams LS, Hingtgen CM (2000) Cerebrovascular disease in pregnancy.  Continuum 6:79-98.

Hingtgen CM, Roos KL. (2001) Clinical trial in central nervous system infections. In: Clinical Trials in Neurologic Practice (Biller J, Bogousslavsky J, eds) pp 237-260.  Boston: Butterworth Heinemann.

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