Chase Hulderman

Chase Hulderman

Greater Milwaukee
1K followers 500+ connections

Activity

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Experience

Education

Licenses & Certifications

Volunteer Experience

  • President

    Student Government Association - Rutgers Medical School

    - 1 year

    Education

    Provided oversight for all student organizations and developed new initiatives. Organized board and general meetings. Administered existing activities, programs, and budgets.

  • Student Doctor

    The Promise Clinic

    - 1 year 10 months

    Provided healthcare for the local indigent and homeless in New Brunswick, NJ as part of a team of medical students.

  • Steering Committee

    The Promise Clinic

    - 1 year 11 months

    Health

    Facilitated communication between subcommittees. Implemented collection of quality metrics and improved clinic efficiency and effectiveness. Designed and created the clinic’s annual report.

Publications

  • Substituent effects on the amination of racemic allyl carbonates using commercially available chiral rhodium catalysts

    Tetrahedron Letters

    In the presence of commercially available chiral rhodium catalysts, a competitive benzylamination of racemic allyl carbonates, substituted with p-X-Ph groups, shows that the reaction proceeds faster with substituents (X) that are more electron-withdrawing. Mechanistic implications of these results are discussed.

    Other authors
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  • RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma

    PNAS

    Neuroblastoma is a childhood cancer that is often fatal despite intense multimodality therapy. In an effort to identify therapeutic targets for this disease, we performed a comprehensive loss-of-function screen of the protein kinome. Thirty kinases showed significant cellular cytotoxicity when depleted, with loss of the cell cycle checkpoint kinase 1 (CHK1/CHEK1) being the most potent. CHK1 mRNA expression was higher in MYC-Neuroblastoma-related (MYCN)-amplified (P < 0.0001) and high-risk (P…

    Neuroblastoma is a childhood cancer that is often fatal despite intense multimodality therapy. In an effort to identify therapeutic targets for this disease, we performed a comprehensive loss-of-function screen of the protein kinome. Thirty kinases showed significant cellular cytotoxicity when depleted, with loss of the cell cycle checkpoint kinase 1 (CHK1/CHEK1) being the most potent. CHK1 mRNA expression was higher in MYC-Neuroblastoma-related (MYCN)-amplified (P < 0.0001) and high-risk (P = 0.03) tumors. Western blotting revealed that CHK1 was constitutively phosphorylated at the ataxia telangiectasia response kinase target site Ser345 and the autophosphorylation site Ser296 in neuroblastoma cell lines. This pattern was also seen in six of eight high-risk primary tumors but not in control nonneuroblastoma cell lines or in seven of eight low-risk primary tumors. Neuroblastoma cells were sensitive to the two CHK1 inhibitors SB21807 and TCS2312, with median IC(50) values of 564 nM and 548 nM, respectively. In contrast, the control lines had high micromolar IC(50) values, indicating a strong correlation between CHK1 phosphorylation and CHK1 inhibitor sensitivity (P = 0.0004). Furthermore, cell cycle analysis revealed that CHK1 inhibition in neuroblastoma cells caused apoptosis during S-phase, consistent with its role in replication fork progression. CHK1 inhibitor sensitivity correlated with total MYC(N) protein levels, and inducing MYCN in retinal pigmented epithelial cells resulted in CHK1 phosphorylation, which caused growth inhibition when inhibited. These data show the power of a functional RNAi screen to identify tractable therapeutical targets in neuroblastoma and support CHK1 inhibition strategies in this disease.

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