Aastha Sindhwani, Ph.D.
Associate Research Scientist Neuroscience & Cell Biology
Yale University, Department of Neuroscience, Wu Tsai Institute Alexion Headquarters, 100 College Street, New Haven, CT 203-***-**** ***************@*****.*** ******.*********@****.*** ResearchGate ORCID Research Profile
Highly organized and meticulous Associate Research Scientist with over six years of research experience at Yale School of Medicine. Specializes in neuroscience and cell biology, with deep expertise in dissecting molecular mechanisms of human brain development and evolution, elucidating lysosomal dynamics in neurodegeneration, and characterizing host–pathogen interactions. Proficient in single-nucleus multiomic profiling (snRNA-seq, snATAC-seq), advanced confocal/Airyscan microscopy, human iPSC differentiation (i Neurons), CRISPR-Cas9 genome editing, quantitative proteomics, and in vivo mouse models. Methodical and detail-oriented, excels at experimental design, data integration, and troubleshooting complex protocols. Collaborative team player and effective communicator, adept at mentoring junior scientists, presenting findings, and fostering interdisciplinary partnerships. Seeking a Staff Scientist or Senior Research associate position to implement rigorous experimental programs, foster interdisciplinary collaboration across biological systems, and translate findings into novel therapeutic strategies.
Education
• Ph.D., Cell Biology Indian Institute of Science Education and Research (IISER), Mohali, India 2019
o Thesis: Discerning the role of a lysosomal tethering factor in promoting the intravacuolar replication of Salmonella
• M.Sc., Medical Biotechnology Post Graduate Institute of Medical Education and Research (P.G.I.M.E.R), Chandigarh, India 2012
o Dissertation: Characterization of the role of Vitamin C in Cancer pathogenesis
• B.Sc. (Hons.), Biomedical Sciences Bhaskaracharya College of Applied Sciences, University of Delhi, India 2010
Research Experience
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Associate Research Scientist Yale School of Medicine, Dept. of Neuroscience & Wu Tsai Institute, New Haven, CT 2022 – Present
• Designed and executed single-nucleus RNA-seq and ATAC-seq experiments on human and non-human primate brain tissue, resolving cell-type–specific transcriptional and chromatin landscapes that distinguish conserved from primate and human-specific regulatory programs.
• Collaborated effectively within interdisciplinary teams, integrating cellular and molecular findings with multi-omic signatures to provide novel insights into the unique aspects of human brain development and evolution and their potential links to neurological disorders.
• Designed and executed advanced imaging experiments utilizing confocal and Airyscan microscopy to delineate complex neuronal processes and synaptic structures in primate tissue and primary neuronal cellular models.
• Established and characterized primary rodent neuronal cultures and iPSC-derived neuronal models relevant to human brain development studies, enabling morphometric and mechanistic investigations of human-specific gene function by quantifying neuronal differentiation and circuit maturation.
• Led critical experimental design, execution, and data analysis for a collaborative project on human cerebellum development, culminating in a co-author manuscript currently under review at Cell. My contributions included.
• Generate and manage transgenic mouse models: colony maintenance, genotyping, intracranial injections, and histological analysis to evaluate in vivo effects of targeted gene perturbations on synapse formation and neuroanatomical architecture. Postdoctoral Research Associate Yale School of Medicine, Dept. of Cell Biology, New Haven, CT 2019 – 2022
• Used live-cell fluorescence imaging to quantify axonal and dendritic lysosome motility in iPSC-derived cortical neurons, demonstrating that precise organelle transport is essential for cytoskeletal stability and autophagic flux.
• Generated JIP3-knockout and JIP4-knockout / endogenously tagged cell lines using CRISPR-Cas9, enabling structure–function analyses of lysosomal motor-adaptor complexes.
• Identified and characterized a novel JIP3/JIP4–interacting protein that regulates microtubule-dependent lysosomal transport; its loss induced lysosomal accumulation, cytoskeletal disorganization, and stalled autophagic intermediates—phenotypes reminiscent of neurodegenerative pathology.
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• Integrated quantitative proteomics with biochemical interaction mapping to elucidate molecular complexes governing lysosomal localization and neuronal homeostasis. Senior Research Fellow (Ph.D. Research) Indian Institute of Science Education and Research
(IISER), Mohali, India 2012 – 2019
• Discovered that the Salmonella effector SifA co-opts and recruits the host endolysosomal trafficking machinery to the Salmonella-containing vacuole (SCV), to promote intracellular survival and establish its replicative niche.
• Performed targeted knockdown of host endo-lysosomal trafficking genes via RNAi/shRNA and applied confocal/live-cell imaging to monitor SCV maturation, LAMP1-positive membrane recruitment, and Rab GTPase dynamics in infected RAW264.7 macrophages and HeLa cells.
• Mapped effector–host interactions by co-immunoprecipitation and immunoblotting, defining HOPS-mediated SCV tethering to lysosomal compartments providing significant new understanding of Salmonella pathogenesis and host cell subversion strategies.
• Quantified intracellular bacterial load via gentamicin-protection assays linking trafficking perturbations to innate immune responses.
• Co-authored a publication demonstrating Arl8b-SKIP-dependent assembly of the HOPS complex on lysosomal membranes, elucidating mechanisms of late endosome–lysosome fusion and cargo trafficking.
Technical Skills
The following table summarizes key technical skills: Category Specific Skills/Techniques Software/Instruments Microscopy
& Imaging
Confocal Microscopy, Airyscan High-Resolution
Imaging, Live Cell Imaging (FRAP, 3D time-lapse,
cargo-trafficking assays), Immunofluorescence
(IF), Immunohistochemistry (IHC)
Leica SP8, Zeiss LSM
series (e.g., LSM 880
with Airyscan),
ImageJ/Fiji, Imaris,
CellProfiler, Nikon SoRa
Cellular &
iPSC
Technologies
Mammalian Cell Culture (immortalized lines,
primary neurons, BMDMs), iPSC Maintenance,
Expansion & Directed Differentiation (i Neurons),
CRISPR-Cas9 Genome Editing (KO, KI,
Standard cell culture
incubators, biosafety
cabinets,
electroporators,
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Endogenous Tagging), Stable Cell Line
Generation (Lentivirus, PiggyBac), Transfection
(Lipofection, Electroporation), RNA Interference
(siRNA, shRNA)
lentiviral production
systems
Molecular
Biology
Molecular Cloning (Plasmid design &
construction, restriction/ligation cloning,
NEBuilder HiFi DNA assembly), DNA/RNA
Isolation & Purification, PCR & Real-time qPCR,
cDNA Synthesis, Site-Directed Mutagenesis,
Western Blotting, Co-Immunoprecipitation (Co-
IP), Yeast Two-Hybrid, Tandem Affinity Purification
(TAP)
Thermal cyclers, gel
electrophoresis systems,
spectrophotometers
(e.g., NanoDrop),
chemiluminescence
imagers (e.g., Bio-Rad
ChemiDoc)
Biochemistry
Recombinant Protein Expression & Purification
(Bacterial, mammalian systems; Epitope Tagging,
Affinity Chromatography (Ni-NTA, GST), Pull-
Down Assays, Density-Gradient
Ultracentrifugation, Organelle Isolation
(Lysosomes, phagosomes)
Beckman coulter
ultracentrifuges
Animal
Models &
Tissue
Analysis
Mouse Colony Management (Breeding,
Weaning, Genotyping), Stereotaxis surgery, Brain
Tissue Dissection) primate tissue handling,
Tissue Processing (Cryopreservation, Paraffin
Embedding), Cryostat/Microtome Sectioning,
Histology (H&E, Nissl), In situ hybridization
(ISH/FISH), IF/IHC on tissue sections
Cryostats, microtomes,
vibratomes, slide
scanners
Microbiology
Bacterial Culture & Manipulation (Salmonella
typhimurium), In Vitro Infection Assays (Cell lines, BMDMs), Colony Forming Unit (CFU) Assays,
Bacterial Knockout Strain Creation (e.g., lambda
red recombineering)
BSL2 cabinets, Shaking
incubators,
spectrophotometers
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Data
Analysis &
Software
Quantitative Image Analysis, Statistical Analysis, Interpretation of IP-Mass Spectrometry data,
Experimental Design, Troubleshooting
GraphPad Prism, FlowJo,
ImageJ/Fiji, Imaris,
MATLAB (basic), Python
(basic scripting for data
analysis), MS Office
Suite (Word, Excel,
PowerPoint), Electronic
Lab Notebooks (e.g.,
eLIMS, Benchling,
LabArchives)
Publications
• Kim SK*, Cherskov A*, Sindhwani A, Choi SH, et al. (Under Review). Human-specific features of the cerebellum and ZP2-regulated synapse development. Cell. (*Equal contributions)
• Sindhwani A, Arya SB, Kaur H, Jagga D, Tuli A, Sharma M. (2017). Salmonella exploits the host endolysosomal tethering factor HOPS complex to promote its intravacuolar replication. PLoS Pathogens, 13(10):e1006700.
• Khatter D*, Sindhwani A*, Sharma M. (2015). Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology. Cell Logistics, 5(3):e1086501. (*Equal contributions; Cover image selected for the issue)
• Khatter D, Raina VB, Dwivedi D, Sindhwani A, Bahl S, Sharma M. (2015). The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes. Journal of Cell Science, 128(9):1746-61.
• Sindhwani A, Muthusammy S, Bhatia A. (2019). Vitamin C may exert variable effects on viability and proliferation of HeLa cells exhibiting high and low chromosomal instability. Advances in Clinical and Experimental Medicine, 28(1), 19-24. Selected Presentations
• Invited Talk: "Molecular Dissection of Salmonella-Host Interactions: The HOPS Complex Hijack." Cell Biology of Infections Seminar, National Centre for Biological Sciences (NCBS), Bangalore, India (October 2016).
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• Oral Presentation: Research Seminar Series, Department of Biological Sciences, IISER Mohali, India.
• Poster Presentation (Awarded): "The HOPS Complex: A Pivotal Host Factor Hijacked by Salmonella for Intracellular Survival." Research Convention, Panjab University (2015).
• Poster Presentation: "The HOPS Complex: A Pivotal Host Factor Hijacked by Salmonella for Intracellular Survival." EMBO Conference: Endocytic Trafficking in Health and Disease, Serock, Poland (September 2017).
• Poster Presentation: "Elucidating Salmonella typhimurium's Strategies to Manipulate Host Lysosomal Pathways." Indian Congress of Cell Biology (ICCB) - A joint meeting of ISCB, IFCB, and APOCB, Hyderabad, India (January 2018).
• Poster Presentation: All India Cell Biology Conference (AICBC), Kerala, India (December 2015).
• Poster Presentation: Wellcome Trust-DBT and IISER Mohali International Symposium:
"Cells to Cellular Programming," Mohali, India (2016) Awards, Honors & Fellowships
• International Travel Support, Science and Engineering Research Board (SERB), Government of India (2018, for EMBO Conference "Endocytic trafficking in health and Disease," Serock, Poland, 2017).
• Best Poster Award, Research Convention, Panjab University (2015).
• Senior Research Fellowship (Ph.D. Fellowship), University Grants Commission (UGC), Government of India (2012-2019).
• All India Rank 14, Graduate Aptitude Test in Engineering (GATE) - Life Sciences (2012). Leadership, Mentorship & Engagement
Academic Leadership:
• Treasury Coordinator, Yale Postdoctoral Association (2021)
• Member, Yale Neuroscience Postdoctoral Committee (2023–present) Peer Review & Symposium Participation:
• Judge, New Haven Science Fair (2023)
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• Co-moderator, Cell and Developmental Biology Session, Indian Congress of Cell Biology
(ICCB)—joint meeting of ISCB, IFCB, and APOCB, Hyderabad, India (January 2018)
• Volunteer, Yale Neuroscience Retreat (2023)
Professional Development:
• Active participation in professional development workshops hosted by the Poorvu Center for Teaching and Learning, Yale University (2021–present) Mentorship:
• Mentored and supervised undergraduate students in Yale’s STARS program, providing training in experimental design, confocal microscopy, molecular biology techniques, and data analysis, thereby fostering independent scientific thinking (2019–2022).