NE CENTER FOR NEUROLOGICAL DISORDERS Group Members Tsuneya Ikezu - Dept of Pharmacology - UNMC Yutong Liu -Dept of Radiology - UNMC Li Tan - Engineering.

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NE CENTER FOR NEUROLOGICAL DISORDERS Group Members Tsuneya Ikezu - Dept of Pharmacology - UNMC Yutong Liu -Dept of Radiology - UNMC Li Tan - Engineering Mechanics - UNL Luwen Zhang - Virology Center - UNL David Holtzclaw - Dept of Physiology - UNMC Yazen Alnouti - Dept. of Pharmaceutical Sci - UNMC Ron Cerny - Dept. of Chemistry - UNL David Berkowitz - Dept of Chemistry - UNL

Charge: Your task is to develop core ideas/projects for an $8-10M ($ M per year for 5 years) NIH Center proposal. Specifically, you should consider the following questions

Briefly describe the core projects your group would design for the Center. Please dream big. Alz-Novel Druggable Target 1:Identification of the first inhibitors for Tao-Tubulin Kinases (TTBK) I and II (I-Alzheimers, II-Spinocerebellar ataxia) -Ikezu Alz-Novel Druggable Target 2:Identification of the first inhibitors for Serine Racemase (hSR) (Alzheimers, stroke)-Berkowitz CNS-Lymphoma: Interferon Regulatory Factor-4 (IRF4) as novel transcription factor/emerging lymphoma target-Zhang Novel Approaches to Neuro-Imaging Use of Mn-, Gd- and Fe-based paramagnetic contrast agents for neuro-MRI (50 uM resolution/stroke model) -Liu, fluorescence with novel self-assembled agents- Tan Drug Metabolism/Optimization Cyt-P450-based drug candidate metabolism - hot spot/byproduct identification by LC/MS-Alouti, Cerny

Identify the key faculty from from both campuses to involve in these projects. Include their strengths. (UNMC on next slide) UNL FacultyStrengths David BerkowitzEnzyme Inhibitor Development Li TanNovel Fluorescent Materials Ron CernyNE Proteomics Center Director Luwen ZhangNE Virology - Lymophoma Pat DussaultMedicinal/Natural Prod Chem James Takacs Medicinal/Natural Prod Chem

Identify the key faculty from from both campuses to involve in these projects. Include their strengths. UNMC Faculty Strengths Tsuneya IkezuNeurodegen Disorders Howard GendelmanNanomedicine Yazen AlnoutiDrug Metab/Pharmacokinetics Yutong LiuRadiology/MRI David HoltzclawFluid Mechanics Hong SunRat Stroke Model (Physiol)

Identify external academic partners & expertise or equipment resources/strengths that are needed to accomplish these projects. Harvard Neurodegenerative Disorder Program (High throughput drug screening) UNMC MRI Center ( Liu) NE Center for Proteomics (Cerny) KU cpd library & HTS facility (Scott Wier)

List potential industry/foundation partners (think broadly) and what they would contribute. Include reasons why they would be interested. Neumedix - Australia/Cayman Islands (VC interest in TTBK inhibition with Prof. Ikezu) Merck, Wyeth-Pfizer, Astrazeneca, GSK, BMS (Drug development for Alzheimers, stroke and CNS-lymphoma)

Describe how you would link the Center to other campus resources.