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I bring in-depth molecular, cellular, and cancer biology expertise and post-graduate experience, to teams-based, fast-moving biotechnology and academic lab settings. I am a recognized leader in the arena of DNA damage repair. As small group lead, I cultivate a culture of camaraderie, cross-functional team investment, and flexibility to achieve team and corporate milestones.As RNA Therapeutics Core Lab Manager, I provide both operational and experimental support to a small team bringing best-in-class circular RNA products to academic and biotech communities of greater Boston and beyond.I provide experimental support to early-stage companies (CellTech Discovery Group LLC, sole proprietor). Experimental or direct support to target/delete genes of interest, Lonza Nucleofector and DNA repair expertise provided.In small biotech, I produced unique cell-based tools, supporting preclinical, selectivity and MOA studies. I develop unique molecular biology tools and cell-based assays focused on preclinical discovery. I established a CRISPR platform for rapid target validation, PD biomarker evaluation, and de-risking studies. Various reporter and target engagement assay development critical to SAR.At BILH/HMS, I pioneered the Ter reporter revealing the role of the tumor suppressor BRCA1 in stalled replication fork repair regulation (Willis, Nature 2014). I discovered BRCA1 suppresses mutagenic tandem duplications which are unique to flawed fork repair, a biomarker for BRCA1 dysfunction in breast and ovarian cancers (Willis, Nature, 2017).Technical Skills• Molecular/cellular biology: CRISPR KI/KO, vector design, RT & qPCR, 2D Southern, DNA/RNA/protein gel electrophoresis, immunoblotting, nucleofection, lipofection, viral transduction, target degradation (AiD/SMASh)• Flow cytometry/microscopy: IF, ICC, cell cycle analysis, multicolor rapid quantitative functional assay development, rare population sort• Tissue culture: primary, immortalized and cancer lines, mouse embryonic fibroblast and stem cell lines• Software: Snapgene, GraphPad Prism, Flowjo, CytExpert/FACS Diva, Cometscore, MS Office• Hardware: Cytometers (MACSquant, LSR, Cytoflex), Integra, Incucyte, Citation 5/Multi-flo, Evos, PC/Mac building/repair, 3d printingFunctional skills: scientific presentation & writing, SOP development Leadership skills: team-building and individual empowerment, small group leadComplete Bibliography: https://www.ncbi.nlm.nih.gov/myncbi/1T1dadzTutz5k/bibliography/public/
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Principal ScientistTasca TherapeuticsBoston, Ma, Us
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Rna Therapeutics Core Manager, Gene And Cell Therapy InstituteMass General Brigham Feb 2024 - PresentSomerville, Massachusetts, UsAs RNA Therapeutics Core Lab Manager, I provide both operational and experimental support to a small team bringing best-in-class circular RNA products to academic and biotech communities of greater Boston and beyond.Bench Scientist Duties: support development of new processes for RNA and LNP asset production, circRNA product functional validation and characterization. Molecular and cellular biology support to the RTC team and visiting entrepreneurs in residence.Core Manager Duties: day to day operations control, CapEx equipment purchase and onboarding, consumable supply and stock management, tissue culture surveillance and standard lab practice enforcement, facilitate sample intake and tracking, working group member for GMP facility buildout, GCTI team checkin. -
Consultant, Bench Scientist, Molecular And Cellular BiologistCelltech Discovery Group, Llc Oct 2023 - PresentI provide molecular and cellular biology expertise and on-site experimental design and support as needed, augmenting client company in house teams. Activities include new target identification, target validation, platform support, MOA studies initiation, and execution of various endpoint assays. Hardware provided: Lonza nucleofector 4D and X-unit.I have worked with seed and small biotech companies on experimental design to delete improve use of CRISPR technology to delete or target genes of interest or provided direct bench support to study MOA of lead assets using a combination of chemical genetics and molecular biology tools (Nexo Tx and Tasca Tx).
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Platform Group Lead | Principal ScientistCyteir Therapeutics Aug 2021 - Feb 2023Lexington, Ma, Us• Managed/trained direct hires (senior scientist and RA) expanding Platform capability and capacity.• Established in house CRISPR mediated gene-editing platform supporting all pre-clinical research.• CRISPR Platform crucial to rapid and robust target validation and de-risking studies, pharmacodynamic biomarker candidate evaluation, and target selectivity assays for CYT-0851 (clinical stage MCT1 inhibitor).• Engaged in CYT-0851 MOA studies using a variety of cell-based assays and internally developed genetic tools.• Established a variety of cell-based assays to measure DNA DSB repair efficiencies, DNA repair protein responses, and physical measurement of DNA damage.• Developed a unique target engagement assay critical to chemistry SAR and screening in support of new target program nomination (MMEJ repair protein Pol Theta, POLQ).• Established in house DNA damage quantification assay (comet assay) to characterize lead chemical matter across the DNA Damage Response (DDR) pipeline. • Managed flow cytometer operation, expansion and training.• Liaised closely with CROs developing molecular biology reagents for cell-based assays. • Liased with CRO initiating siRNA screens to expand potential indications for preclinical programs or to generate reagents important to nascent programs.• Core member of target identification working group; new target ID/evaluation, followed by genetic validation and de-risking studies.• Core member pipeline working group; 20+ IP in-licensing evaluation with data room due diligence.• Summarized data, Platform objectives and technology development routinely to project & management teams. -
Staff Scientist (Cancer Center)Beth Israel Lahey Health Dec 2014 - Jul 2021• Conceptualized projects leading to $2M funding and publications in PLoS Genetics, NSMB, & Nature, STAR Protocols, Current Opinions Genetic Development, Molecular Cell, Methods in Molecular Biology.• Trained incoming staff: two postdoctoral fellows, one assistant in tissue culture.• Identified DNA tandem duplications (TD) as a biomarker of BRCA1 loss in cancer.• Defined a protein network regulating TDs revealing the mechanism of TD formation.• Expanded the Tus/Ter HR reporter system toolset with 24+ reporter variant lines.• Generated Tus/Ter reporter in human immortalized and cancer-derived cell lines.• Completed an initial siRNA-screen exploring the roles of ~210 target genes in stalled fork repair.• Established CRISPR/Cas9 plasmid, in-house sgRNA transcription, and RNP use to delete/point mutate/tag target genes in ES cells.• Utilized CRISPR/Cas9 for use in molecular cloning, and as a nuclease to induce site-specific HR/repair repair in vitro.• Completed a survey of 292 BRCA1 VUS ("variants of uncertain significance") alleles for rescue of BRCA1-mutant cell HR repair defects and PARP inhibitor sensitivity in collaboration with Dr. Jonkers group (NKI).• Provided data critical for ongoing and completed patent applications. -
American Cancer Society Postdoctoral FellowBeth Israel Deaconess Medical Center Jul 2012 - Nov 2014Boston, Ma, Us• Produced key data for $1.5M grant funding and publications in PNAS, PLoS Genetics, Trends in Cancer, Molecular Cell, Nature Communications, and Nature.• Patent issued: screening of BRCA1 variants of uncertain significance, USPTO #10697026• Optimized and validated cell model systems to measure DNA DSB repair.• Established 2D Southern blotting measuring Tus/Ter-induced replication fork stalling.• Evaluated the roles of Fanconi Anemia gene family proteins, BRCA2, and RAD51 in stalled fork repair.• Provided critical data for RO1 and R21 funded applications focused on BRCA1 VUS alleles' HR repair defects and chemotherapeutic sensitivities. -
National Cancer Institute Nih Postdoctoral Research FellowBeth Israel Deaconess Medical Center Sep 2010 - Jun 2012Boston, Ma, Us• Pioneered/validated the Tus/Ter stalled fork repair reporter to quantify homologous recombination (HR) induced by site-specific replication fork stalling on the mammalian chromosome.• Revealed a key regulatory role for BRCA1 in stalled fork repair.• Optimized and validated cell model systems to measure DNA DSB repair.• Established 2D Southern blotting to quantify replication intermediates upon Tus/Ter-triggered fork arrest.
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Postdoctoral Associate (Rhind Lab)University Of Massachusetts Sep 2009 - Sep 2010Boston, Massachusetts, Us• Utilized DNA combing to explore checkpoint-dependent regulation of replication origin firing and replication fork rate in response to MMS, hydroxyurea, and bleomycin.• Explored the role of PCNA SUMO and ubiquitin modifications in replication slowing in response to MMS. -
Research Assistant (Tyler Jacks' Lab)Massachusetts Institute Of Technology Sep 1999 - Jun 2002Cambridge, Ma, Us• Developed murine models of human cancers with Dr. David Tuveson in Dr. Tyler Jacks' lab.• Engineered stem cells and mice carrying Cre-LoxP mediated conditional mutant alleles of the tumor suppressors p53 and K-ras.• Measured p53 and K-ras mutant contribution to cancer development using mouse aging studies.• Determined impact of these mutations on cell physiology and behavior in mouse fibroblasts in vitro and in vivo.• Investigated and published on the efficacy of STI571 (Gleevec) treatment on GIST primary cells in vitro.• Published several papers describing mutant mice as models for human pancreatic and lung cancers. -
Research Assistant (Achim Gossler'S Lab)The Jackson Laboratory Sep 1997 - Aug 1999Bar Harbor, Me, Us• Explored the mechanisms of vertebral column formation during mouse development. • Generated detailed genetic maps for three spontaneous mutations affecting axial patterning and skeletal formation, specifically Danforth's shorttail (Sd), Pintail (Pt), and Truncate (Tc). -
Research AssistantUniversity Of Maine Jun 1997 - Jul 1997Orono, Me, UsAssisted Dr. Dorothy Croall characterizing the protease calpain and its role in calcium-dependent cellular functions. Synthesized cDNA libraries from total RNA (produced by starving cultures of Dictyostelium discoideum) and screened those libraries for homologues to murine calpain. -
Nsf Undergraduate Research FellowUniversity Of Maine May 1996 - May 1997Orono, Me, Us• Constructed a mutant gene library to characterize G-protein signaling pathway(s) essential for the completion of the life cycle of the slime mold Dictyostelium discoideum.• Capstone, senior research project characterizing several mutants of the G protein subunit Ga2 in signaling.
Nicholas Willis Skills
Nicholas Willis Education Details
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Umass Chan Medical SchoolBiomedical Sciences -
University Of MaineBiochemistry
Frequently Asked Questions about Nicholas Willis
What company does Nicholas Willis work for?
Nicholas Willis works for Tasca Therapeutics
What is Nicholas Willis's role at the current company?
Nicholas Willis's current role is Principal Scientist.
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What schools did Nicholas Willis attend?
Nicholas Willis attended Umass Chan Medical School, University Of Maine.
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Nicholas Willis has skills like Genetics, Molecular Biology, Molecular Cloning, Protein Chemistry, Cell Culture, Cell, Western Blotting, In Vitro, Cell Biology, Transfection, Dna, In Vivo.
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