• In charge of nucleic acid therapeutic programs in Ultragenyx, including multiple mRNA, siRNA and antisense therapeutic projects in rare diseases. Involved in new project concept formation, proposals and prioritization, candidate sequence design and optimization, delivery strategy selection and verification, POC study design and milestone and stage-up criteria. • Lead nucleic acid therapeutic platform research to plan and identify strategies to improve and expand current nucleic acid therapeutic opportunities. Improve the current nucleic therapy and delivery platform. Explore novel technology in both industry and academia, and conduct feasibility studies for due diligent and verification.• Evaluate external nucleic acid therapeutic projects and technology business opportunities, and providing scientific opinion of various gene therapies strategies. Provide scientific investigation for FTO and partner IP evaluation.• Project team lead for multiple mRNA based therapeutic projects for rare genetic diseases with external business partner. Recently transfer one therapeutic program to development in preparation for IND. • Manage an internal research team to establish and execute in vitro/ex vivo cell based assays and immune stimulation assays to select and rank order drug candidates, and guide lead optimization effort. Collaborate with internal development team and external collaborators in various stages and disease areas, including identifying and manage CRO activities.

• Lead oligonucleotide platform research for target validation and drug development programs, and manage resource and research activities of all RNAi/antisense projects. • Maintain current knowledge on oligonucleotide platforms (siRNA/antisense/mRNA/lncRNA/aptamer), gene editing and expression profiling technology.• Established oligonucleotide research platform for delivery strategies, target validation and lead identification for oligonucleotide drug development programs, including transfection (attach and suspension cell lines and primary cells), target knockdown detection, in vitro/in vivo uptake, cell based functional assay, and lead identification. • Initiated target discovery projects with RNAi based screen, RNA-seq and miRNA profiling to generate and prioritize potential targets. Proposed and initiate new targets for oligonucleotide and antibody based therapeutics programs in immunology.• Managed PhD/MS/BS level scientists and internal resources in highly matrix environment and identified and established external collaborations (CROs and academia) to support project timeline to reach Go/No Go decision. Conducted consultation with KOLs on selected targets.

• Lead in vitro assay development, optimized HTS screening process, investigate IVIVC for oligonucleotide therapeutics, and developed surrogate target for delivery studies.• Optimized in vitro cell based assay SOP for target validation and siRNA lead identification for oncology and metabolic diseases in HTS format• Built flow cytometry based apoptosis assays for functional screening for oncology therapeutics program• Utilized multiplex luminex technology for biomarkers, pathway analysis, and off-target effect in target validation and functional screening for oligonucleotide therapy• Built and validated oligonucleotide functional delivery platform with universal target based by FACS• Evaluated of 2D and 3D in vitro models for antisense toxicology investigation and IVIVC analysis• Worked with various therapeutic areas and academic laboratories to validate targets and identified potential therapeutic opportunities amiable for siRNA and ASO compounds to launch project teams• Managed both PhD/MS/BS reports, contributed to various functional groups and therapeutic teams, and established and managed external collaborations

• Lead proof-of-concept RNAi therapeutic project in Immunology and identified novel peptide based transfection reagents for siRNA, conducted DOE studies with trans-well cell based assay to prolong PK/PD effect, and manage internal and external studies to support ANDA filing. • Built high throughput cell based siRNA delivery assay using flow cytometry (FACS) and Image Stream, and screened novel siRNA transfection reagents• Designed and set up ex vivo human and mouse monocyte isolation and cell based knock down assay for TNF-a target, and designed and screened siRNA for TNF-a as POC study• Implemented b-gal reporter gene in 9L/LacZ cell lines and GFP reporter gene in primary cells for siRNA knock down assay• Evaluated different in vivo models for TNF-a target and transgenic reporter (GFP) model and manage CROs to conduct in vivo studies• Designed and set up Luminex xMAP based multiplex assay for cytokins detection for siRNA knockdown and off-target analysis• Modified and screened siRNAs to enhance the efficacy, improved serum stability, and reduced off target effect of siRNAs, and participated in microarray analysis of off-target study• Managed external collaboration with clinicians to conduct siRNA knock down studies with Rheumatoid Arthritis patient populations• Set up bioanalytical GPCR based cAMP stimulation cell based assay in SaoS-2 cells for characterization of Parathyroid Hormone• Performed DOE with trans-well permeation cell based assay using EpiAirway culture, using HPLC and ELISA as bioanalytical methods• Conducted PK/PD studies in animal models to verify in vitro results and optimize formulations to modify PK/PD profile• Managed experiments with CROs to address FDA immunogenicity concerns of aggregation of biologic therapeutics in formulations, including SEC, AUC, FFF, CD, NMR, and BIACORE.

Lead study on identifying mutations in patient with Progeria and conduct proof-of-concept study to correct cellular phenotype by shRNA, and managed the project on genetic polymorphisms discovery on aged US population, and independently working on structure and function study of WRN protein.• Implemented FACS cell based reporter gene (GFP/YFP) assay and V(D)J recombination assay for both homologous and non-homologous DNA double strand break repair function analysis by transfection of tissue culture cells• Characterized various mutant forms of WRN through baculovirus expression for protein stability and DNA repair function through cell based assay• Managed SNPs discovery in SOD2, ApoE, and WRN genes in US elderly population, and set up RNA alternative splicing assay to decipher the function of the SNPs in introns.• Identified dominant negative SNPs in LMNA gene of patients of Progeria disease and identify cellular phenotype• Constructed lentivirus based siRNA expression vectors to express siRNA to overcome the cellular phenotype in the transfected cells from Progeria patients

• Interactive cloning of factors in pathogen (Agrobacterium tumefaciens) and hosts(Arabidopsis thaliana and yeast) by yeast two hybrid, and further demonstrate that VirE1 functions as molecular chaperone for VirE2 and identify interaction of virulence protein with host cyclophilins• Investigate the secretion of virulence proteins from pathogen to host and identify an putative secretion pathway for virulence proteins and efforts to dissect the virulence secretion process• Participate in the genome sequencing project of Agrobacterium tumefaciens among UW Microbiology, Genome Center, University of Campisi, and DuPont• Design and implement the marker exchange technique to create unmarked deletion mutants to Identify bacterial secretion system and extracellular appendages in Agrobacterium tumefaciens • Attained Oracle Certified Java Programming and Oracle Professional Web Developer Program• Manage the laboratory strain inventory and external requests on constructs and strains

• Set up yeast functional complementation assay to clone novel amino acid transporters in Arabidopsis thaliana (cDNA expression constructs), and further modify the yeast growth conditions to identify amino acid transporters with different substrate affinity• In silica cloning of Arabidopsis thaliana amino acid transporters by bioinformatics sequence analogy screening, and verify its transport function by heterologous expression in yeast.• Screen amino acid transport mutants in T-DNA tagged Arabidopsis thaliana library and clone the mutated gene by plasmid rescue• Design and perform both random and site-specific mutagenesis of amino acid transporters for structure and function analysis in yeast• Attained Arabidopsis Molecular Genetics at Cold Spring Harbor Laboratory