Drive therapies towards the clinic with expert preclinical cell-based assay support
Passionate about implementing robust assays and supporting drug discovery to accelerate life-altering therapies to patients
My Services
Flexible arrangements available depending on your project needs. Let’s talk!
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CRO management
design and monitoring of in vitro, ex vivo, in vivo studies
SAR campaign management
assay development, protocol implementation, template creation, data uploading, QC, IND report and patent filing authoring
Phenotypic assays
proliferation, apoptosis, cell cycle, DNA damage
Target engagement assays
in-cell western, NanoBiT, NanoBRET, qPCR, ELISA
Combination studies
Familiar with various databases and ELNs
(CDD Vault, Dotmatics, Arxspan, LiveDesign)
Master of Science in Microbiology, UMass-Amherst
Most recent position : Senior Scientist at NextRNA Therapeutics
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Example of task or project:
Do you have established assays that need data collection, QC, and monitoring?
Do you need a protocol or IND section authored?
Basic service :
~2-5 hours/week of routine work
Short term finite task
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Example of task or project:
Do you need to transfer an assay to a CRO then continue monitoring assay performance?
Do you have a project that requires more hands on guidance of a CRO? Do large datasets need to be processed and next steps decided actively and frequently?
Intermediate service :
~5-10 hours/week
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Example of task or project:
Do you need to transfer an assay to a CRO, continue monitoring performance, then finalize with authoring IND section?
Do you need someone to develop an assay in your lab then transfer to a CRO for screening campaign?
Do you need 3-6 months of full time lab work?
Advanced service :
~10-20 hours/week
40 hours/week for 3-6 months
Research Experience
Highlights
17 years of hands-on research experience
12 years of cancer biology and cell based assay development
Spanning small - large sized companies
Novartis, Aileron Therapeutics, Epizyme, Rome Therapeutics, NextRNA Therapeutics
Contributed to the following FDA-approved or clinical trial therapies:
TAZVERIK, EZH2 inhibitor, for R/R follicular lymphoma
SETD2 inhibitor, granted FDA Fast Track status and is currently under evaluation in a Phase I/Ib trial in adult patients with relapsed or refractory multiple myeloma and diffuse large B-cell lymphoma
Key Contributions:
Responsible for all cellular assay development and SAR campaign for SETD2 program, designed critical studies and generated reports for IND submissions for SET-101 filing
Led preclinical efforts to identify additional indication as part of life cycle management of clinical candidate SETD2 inhibitor EZM0414
Collaborated with numerous project leaders to provide guidance on combination potential of lead program compounds
As a key in vitro biology member of tazemetostat, designed and executed various timely ad hoc studies to support the clinical trials. Designed critical studies and generated reports for IND submissions
Conducted critical experiments in epithelioid sarcoma to support the preclinical package presented at ODAC (Oncology Drugs Advisory Committee meeting) for the vote of approval of tazemetostat
Designed in vivo studies for PK/PD/efficacy and successfully managed through CRO in the context of combination with standard of care and epigenetic inhibitors
Designed studies to understand mechanisms of acquired resistance to standard of care including generation and characterization of in vitro models for TAZVERIK
As the sole in vitro pharmacology scientist at Rome and NextRNA, communicated strategies, plans, timelines, and challenges to core teams, project teams, and leadership. Compiled all necessary cell-based assay data and protocols for patent filings.
Publications and poster presentations
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EZH2 Inhibition by Tazemetostat Results in Altered Dependency on B-cell Activation Signaling in DLBCL
https://pubmed.ncbi.nlm.nih.gov/28835384/
Conformational-Design-Driven Discovery of EZM0414: A Selective, Potent SETD2 Inhibitor for Clinical Studies
https://pubs.acs.org/doi/10.1021/acsmedchemlett.2c00167
Discovery of a First-in-Class Inhibitor of the Histone Methyltransferase SETD2 Suitable for Preclinical Studies
https://europepmc.org/article/med/34671445
Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197372
DOT1L inhibitor EPZ-5676 displays synergistic antiproliferative activity in combination with standard of care drugs and hypomethylating agents in MLL-rearranged leukemia cells
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ASH (2021): Pharmacologic Inhibition of the Histone Methyltransferase SETD2 with EZM0414 as a Novel Therapeutic Strategy in Relapsed or Refractory Multiple Myeloma and Diffuse Large B-cell Lymphoma. J Totman, D Brach, et al.
AACR (2020): Aberrant SWI/SNF complexes lacking SMARCA2 or SMARCA4 differentially affect cell state and response to a novel SMARCA2/4 inhibitor. L Eichinger, C Pantano, V Motwani, D Brach, et al.
AACR (2020): Identification of a potent, orally-available SMARCA2/4 inhibitor with in vitro and in vivo activity in preclinical models of SMARCA4-mutant NSCLC. A Drew, L Eichinger, C Pantano, V Motwani, D Brach, et al.
Triple meeting (AACR, NCI, EORTC) (2019) Synergistic activity of tazemetostat in combination with androgen signaling inhibitors in preclinical models of prostate cancer demonstrates potential for clinical expansion. V Motwani, D Brach, et al.
ASH (2018): Identification of a First-in-Class SETD2 Inhibitor That Shows Potent and Selective AntiProliferative Activity in t(4;14) Multiple Myeloma: T(4;14) Multiple Myeloma Cells Are Dependent on Both H3K36 Di and Tri-Methylation. M Thomenius, J Totman, K Cosmopoulos, D Brach, et al.
Triple meeting (AACR, NCI, EORTC) (2015) EZH2 plays a critical role in B-cell maturation and in nonHodgkin's lymphoma: Interplay between EZH2 function and B-cell activation. D Johnston, D Brach, et al.
Contact
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