Director, DNA-Chromatin Biology

 Job Title:

Science Director – DNA/Chromatin Biology

 

Location: Los Angeles, CA or Princeton, NJ / currently hybrid

 

Vaccination against COVID-19 is a prerequisite for employment at CHDI Management.

 

Job Description:

 

Drug Discovery Scientist with roles and responsibilities in addressing both the local and global role of epigenetics and chromatin regulatory biology as a cause and consequence of Huntington’s disease (HD). Among the many aspects of elucidating the causal drivers of HD, what is non-controversial is the role of the HTT CAG expansion as the root cause. CHDI is emerging a view to increase focus on HTT (CAG)n expansions at the DNA level with aims towards understanding pathogenesis and to identify potential paths towards therapeutic intervention.

The job candidate will manage a portfolio to interrogate and integrate the complex biological events of DNA structure, DNA epigenetic marks, RNA transcription, mRNA splicing, somatic instability and 3-D genomic architecture, evaluating relative contributions across vulnerable cell types in HD.  Expertise in DNA topology, DNA modifications, histone modifications, DNA-protein interactions, DNA transcription both at the gene and genome level would enable a coherent and coordinated effort for further illuminating the regulatory biology of HD.  Expertise and ability to help discern a strategic path forward of current knowledge, oversee academic activities in this biology and address the pivotal questions with new activities/investigators is warranted and needed. Such fundamental knowledge is of high value for a desired knowledge of HD biology as well as being directly relevant to ongoing studies of CAG somatic instability, HTT regulation, mRNA splicing and mode of action of genomic modalities (HTT ASOs, siRNAs, CAG-DNA binding proteins) and potentially small molecule therapies targeting the mutant HTT DNA itself, DNA MMR proteins at HTT,  and potential therapeutic approaches directed at chromatin modifying proteins.

 

Job Responsibilities:

The responsibilities include:

• Science Director and team member in the CHDI Preclinical group; in Thematic Areas including mHTT DNA, RNA, Protein; Somatic Instability/DNA Mismatch Repair (MMR); and non-MMR genome-wide association studies (GWAS).
• Identify, vet, advance and manage an academic funding portfolio aimed at elucidating DNA topology, DNA modifications, histone modifications, DNA-protein interactions, and DNA transcription both at the mHTT gene and genome level.
• Develop de novo HTT transcription assays in suitable cellular model and in vivo systems to investigate impact of interventional agents affecting somatic instability.
• Identify and launch key technologies/assays and collaborators required to enable biophysical evaluation of CAG expanded DNA structure using in vitro, cellular and in vivo model systems in HD.
• Co-lead and collaborate with team members to conceptualize, implement, validate, and integrate assays into an efficient flow scheme for candidates to therapeutic programs.
• Project lead/co-lead for the development and qualification of biochemical, biophysical, and cell-based assays suitable and deployable for drug discovery campaigns targeting the mHTT CAG expanded DNA.
• Collaborate with Platform teams to identify and deliver reagents needed to support mHTT DNA target biology (i.e. Genetically modified animal models, protein production, antibody production, structural biology).
• Co-Lead the development of proof-of-concept tool molecules across a range of modalities (small molecule, RNAi, CRISPR, ZFPs)
• Liaise end enable Biotech and Pharma looking to advance technologies and modalities to target the mHTT DNA, mHTT transcription, mHTT RNA splicing or epigenetic modulation.
• Contribute to development of standard operating protocols for assays and for data qualification and registration.
• Develop and participate in project teams to achieve milestone-based goals to rapidly identify proof-of-concept candidates for cellular and in vivo testing in animal models of HD
• Review and approve detailed reports for each project and campaign in area of responsibility.
• Lead and oversee contract organization scientists for implementation of drug discovery goals.
• Communicate results in presentations at scientific meetings and by co-authoring publications.

 

Requirements:

The candidate of choice will have:

• A PhD in Molecular/Cell Biology, Biochemistry, Biophysics, or Neuroscience or equivalent.
• Proven scientific track record in early drug discovery projects with >5 years in the pharmaceutical/biotechnology sector.
• Experience with DNA biology including DNA structure, DNA epigenetic marks, RNA transcription, splicing, somatic instability and 3-D genomic architecture.
• Rigorous data analyses and interpretation
• Knowledge and experience with industry standard quantitative biology tools, technologies, and vendors.
• Experience in managing external contract research organization collaborations.
• Experience in managing biopharma: academic collaborations.
• Excellent written and oral communication skills
• Demonstrated ability to both lead and be a team player in an interdisciplinary team-oriented environment.

 

Preferred Skills:

An ideal candidate would also have:

• Expertise in the biology and relevant assays for transcription-based mechanisms.
• Experience with establishing target engagement and pharmacodynamic endpoints.
• Evidence of creative problem solving
• Expertise in DNA repair biology
• Bridging biochemical and structural biology in drug discovery programs
• Expertise in working in the CNS and neurodegeneration drug discovery.
• Experience working with a diversity of cell-based assays including stem cells and derivatives.
• A publication track record demonstrating rigor and evidence of cross-functional teamwork.

 

 

About CHDI Foundation, Inc.

CHDI Foundation, Inc. is a privately-funded, not-for-profit, biomedical research organization that is exclusively dedicated to rapidly discovering, accelerating and developing therapies that slow the progression of Huntington’s disease (HD). Our scientists work closely with a network of more than 600 researchers in academic and industrial laboratories around the world in the pursuit of these innovative therapies, providing strategic scientific direction to ensure that our common goals remain in focus. This helps bridge the translational gap that often exists between academic and industrial research pursuits and that adds costly delays to therapy development. In its role as a collaborative enabler, CHDI seeks to bring the right partners together to identify and address critical scientific issues and move drug candidates to clinical evaluation as rapidly as possible. Our activities extend from exploratory biology to the identification and validation of therapeutic targets, and from drug discovery and development to clinical studies and trials. More information about CHDI can be found at www.chdifoundation.org

About CHDI Management, Inc.

CHDI Management, Inc. was established in 2002 to provide administrative, management and grant making services to CHDI Foundation, Inc.

 

 

 

Salary range: $120,000-220,000.  Exact compensation will vary based on experience.

 

Resumes to