Mary Wertz

Development of antisense oligonucleotides (ASOs) for treatment of a genetic neurodegenerative disease. - Third employee, responsible for starting laboratory, hiring and training research staff, and establishing best practices for data generation and documentation in Benchling ELN. - Biology lead on program with the goal of identifying an ASO development candidate. - Supervising internalization of assays from academic collaborators and CROs to reproduce key foundational data. - Leading development of novel in vitro assays in IPSC-derived healthy and FTD-patient neurons and microglia for secondary screens to identify top ASOs for non-GLP tolerability studies. - Spearheading assessment of in vivo target engagement via endpoint PCR, qPCR and mass spectrometry of protein expression. - Managing external CRO interactions to advance primary ASO screening, cell line model generation, and in vivo studies in rodents and NHPs. - Communicating and presenting key findings to Third Rock partners to enable decisions and strategy.

Identification and validation of small molecules for altering expression of root cause genes in genetically defined rare diseases to improve patient outcomes. • Lead a cross-functional project team to validate and advance prioritized targets in a high-value hematological disease. • Developed expertise in hematology, cardiac biology, and high-throughput disease modeling. • Mentored scientists, research associates, and Co-op students to design and execute experiments, analyze results, and present data in project team meetings.

Screening for genetic modifiers of mutant Huntingtin toxicity in the mouse CNS • Developed a novel in vivo screening technique using barcoded lentiviral libraries. • Focused on identification and characterization of genes causing cell-type specific cell death in Huntingtons Disease.

Characterization of aberrant microRNA and mRNA expression in Spinal Muscular Atrophy • Published article "Cell-type-specific miR-431 dysregulation in a motor neuron model of spinal muscular atrophy." to conclude graduate work. • Identified aberrantly expressed microRNAs by LNA-based microarray profiling and validation in in vitro SMN models. • Integrated microRNA:mRNA profiling data to identify miR-431 as a candidate regulator of motor neuron axon length by direct target modulation via 3’UTR binding in a preclinical model of SMA.

Characterization of aberrant microRNA and mRNA expression in Spinal Muscular Atrophy • Identified aberrantly expressed microRNAs by LNA-based microarray profiling and validation in in vitro SMN models. • Integrated microRNA:mRNA profiling data to identify miR-431 as a candidate regulator of motor neuron axon length by direct target modulation via 3’UTR binding in a preclinical model of SMA.

• Worked on elucidating the effect of increased BACE cleavage of voltage-gated sodium channel β2 subunit and ICD release on Nav1.1 alpha-subunit levels and trafficking. • Characterized the role of Familial Alzheimer’s Disease mutations in presenilin1 on γ-secretase activity and metabolism of voltage-gated sodium channel subunit β2. • Presented findings of an independent project at lab meetings and departmental poster sessions.

• Wrote a departmental honors thesis on the characterization of the HPV16 E2 protein nuclear localization sequence. • Created GFP-HPV16E2 expression plasmids with mutations to the suspected NLS for transfection and localization studies.

Researched the effects of caloric restriction on light damage induced apoptosis in mouse retina.