
Krishanu Saha
· ProfessorVerifiedUniversity of Wisconsin-Madison · Biomedical Engineering
Active 1997–2026
About
Krishanu Saha is a professor in the Department of Biomedical Engineering at the University of Wisconsin-Madison. His research interests lie in using human stem cells together with emerging engineering methods in material science and synthetic biology to develop smarter therapeutics, model human disease, and advance personalized medicine. His work encompasses personalized and regenerative medicine, biomaterials engineering, stem cell biology, developmental biology, signal transduction, systems biology, synthetic biology, and the design principles of spatial and temporal control networks in cells. Saha has made significant contributions to the field through his innovative approaches to gene editing, cellular reprogramming, and tissue engineering, and has been recognized with numerous awards and honors for his leadership and research excellence.
Research topics
- Computer Science
- Biology
- Cell biology
- Computational biology
- Chemistry
- Molecular biology
- Physics
- Immunology
- Optics
- Genetics
- Data science
Selected publications
Figshare · 2026-01-01
articleOpen accessSupplemental Document
Figshare · 2026-01-01
otherOpen accessGlioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor patient survival, underscoring the need for novel therapeutic strategies and improved preclinical models. Patient-derived tumor spheroids (PDTSs) offer a physiologically relevant in vitro platform for evaluating treatments such as chimeric antigen receptor (CAR) T cell therapy, chemotherapy, and radiation. However, significant challenges remain in monitoring the complex three-dimensional (3D) microenvironment of the GBM PDTSs. Current imaging techniques used for this purpose are primarily endpoint analyses which lack critical real-time, non-invasive capabilities that ultimately preclude longitudinal and continuous monitoring. In this study, we introduce quantitative Oblique Back-illumination Microscopy (qOBM) as a novel, label-free, and non-invasive imaging approach for longitudinal and continuous, high-resolution monitoring of GBM PDTSs during treatment. qOBM enables real-time visualization of cellular processes, including apoptosis, cell migration, and T cell-mediated cytotoxicity by leveraging tomographic refractive index-based quantitative imaging. We construct a compact qOBM system that fits within common incubators and apply it to study the effects of radiation, chemotherapy, and immunotherapy on three patient-derived GBM cell lines, extracting both static and dynamic image features over a 72-hour treatment period. Additionally, we develop machine learning models to predict spheroid viability and cytotoxicity, demonstrating the potential of qOBM to enhance treatment evaluation. Our findings establish qOBM as a powerful tool for longitudinal and continuous spheroid monitoring, offering a non-destructive, high-resolution alternative to conventional endpoint assays and improving the evaluation of preclinical treatments for GBM.
Brain Research · 2026-05-02
articleOpen accessmicroglia clustered around Aβ plaques, with limited neuronal expression. Bulk RNA sequencing of Rag-5xFAD brain tissue demonstrated enrichment of disease-associated microglia (DAM) and senescence-related transcriptional programs. These findings indicate that uPAR marks a subset of plaque-associated glial cells undergoing functional and transcriptional remodeling in AD, independent of peripheral adaptive immune signaling. Collectively, our results identify uPAR as a marker of dysfunctional, DAM-like microglia and implicate it in senescence-associated neuroinflammatory pathways. This work provides a framework for future studies targeting uPAR-expressing glial populations as a potential therapeutic strategy in AD.
Nanofluid Flow in a U-Tube Double-Pipe Heat Exchanger
2026-02-23
book-chapterDue to their minimal maintenance requirements and simple design, double-pipe heat exchangers have found widespread application. The heat exchangers’ effectiveness can be increased by enhancing the rate of heat transfer, besides reducing their size by using nanofluid. The present study investigates the use of nanofluid on heat transfer and fluid flow in a U-tube double-pipe heat exchanger. Additionally, heat transport in a heat exchanger was examined using numerical modeling. The computational results derived from the currently developed model for water were validated and were found to agree well with the literature. The present model has been further used for heat transfer studies of CuO-PANI (Copper Oxide Polyaniline) nanoparticles in water, flowing in the heat exchanger. According to the study, nanofluids had a higher heat transfer coefficient than water. The overall heat transfer coefficient increased in accordance to the hot liquid’s flow velocity, which varied from 0.05 m/s to 0.20 m/s. This demonstrated that increasing the amount of conductive nanoparticles in water can improve the efficiency of heat transmission. In the future, this model can be used to compare the effectiveness of different heat exchangers and nanofluids. This could aid in the development of more energy-efficient procedures across several industries.
Figshare · 2026-01-01
otherOpen accessGlioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor patient survival, underscoring the need for novel therapeutic strategies and improved preclinical models. Patient-derived tumor spheroids (PDTSs) offer a physiologically relevant in vitro platform for evaluating treatments such as chimeric antigen receptor (CAR) T cell therapy, chemotherapy, and radiation. However, significant challenges remain in monitoring the complex three-dimensional (3D) microenvironment of the GBM PDTSs. Current imaging techniques used for this purpose are primarily endpoint analyses which lack critical real-time, non-invasive capabilities that ultimately preclude longitudinal and continuous monitoring. In this study, we introduce quantitative Oblique Back-illumination Microscopy (qOBM) as a novel, label-free, and non-invasive imaging approach for longitudinal and continuous, high-resolution monitoring of GBM PDTSs during treatment. qOBM enables real-time visualization of cellular processes, including apoptosis, cell migration, and T cell-mediated cytotoxicity by leveraging tomographic refractive index-based quantitative imaging. We construct a compact qOBM system that fits within common incubators and apply it to study the effects of radiation, chemotherapy, and immunotherapy on three patient-derived GBM cell lines, extracting both static and dynamic image features over a 72-hour treatment period. Additionally, we develop machine learning models to predict spheroid viability and cytotoxicity, demonstrating the potential of qOBM to enhance treatment evaluation. Our findings establish qOBM as a powerful tool for longitudinal and continuous spheroid monitoring, offering a non-destructive, high-resolution alternative to conventional endpoint assays and improving the evaluation of preclinical treatments for GBM.
Research Square · 2026-01-29
preprintOpen accessMonitoring biological effects of somatic cell genome editing
Nature Reviews Genetics · 2026-01-13 · 4 citations
articleOpen accessOpen MIND · 2026-01-01
articleSupplemental Document
Molecular Therapy Oncology · 2026-04-07
articleOpen access-CAR T cells without upregulating exhaustion markers (PD-1/LAG3). These findings suggest that in the management of treatment-resistant pediatric solid tumors, utilizing chidamide during the manufacturing of CRISPR-engineered CAR T cells may enhance their persistence while retaining a naive phenotype.
International Journal of Biological Sciences · 2026-04-23
articleOpen accessPoint mutations in the KCNJ13 gene cause autosomal recessive childhood blindness, Leber congenital amaurosis (LCA16), by disrupting Kir7.1 channel function.We describe the etiology of the LCA16 retinopathy phenotype in three patients from two unrelated families harboring a homozygous KCNJ13 missense mutation (c.431T>C, p.Leu144Pro).Our in silico prediction and in vitro validation using a human iPSC-derived retinal pigmented epithelium (RPE) model created via lipid nanoparticle-mediated delivery of the adenine base editor (ABE8e) demonstrated that the L144P mutation impairs Kir7.1 channel function and confirmed that non-viral biologic delivery is clinically translatable.We used two cytosine base editors (CBEs, BE4max-WTCas9 and evoCDA-SpCas9-NG) to correct this mutation in an L144P HEK293 stable cell model, achieving high on-target editing efficiency.However, our electrophysiological measurements showed minimal functional rescue of the channel in CBE-edited cells due to bystander nucleotide editing.Editing with evoCDA introduced a bystander missense mutation (L143F), whereas BE4max primarily generated silent mutations.Extended characterization of BE4max-edited cells revealed a distorted mRNA structure, altered half-life, and reduced abundance of cognate tRNA, all associated with these silent changes.In contrast, prime editing successfully restored channel function.Prime editors targeting the L144P locus achieved approximately 20% on-target editing without introducing bystander nucleotide editing or synonymous changes.Functional assessment demonstrated a strong genotype-phenotype correlation, with restored Kir7.1 channel activity observed in 28% of edited cells (12/43).Overall, these results highlight the importance of comprehensive functional validation of genome editing outcomes and emphasize the need for rigorous preclinical studies to translate therapeutic genome editing into first-in-human trials for genetically diverse diseases.
Recent grants
Enabling Nanoplatforms for Targeted in vivo Delivery of CRISPR/Cas9 Ribonucleoproteins in the Brain
NIH · $1.5M · 2018–2021
Assembly of Novel Gene Editing Particles to Understand Genome Surgery in Patient-Derived Cells
NIH · $370k · 2016–2021
CAREER: Towards Synthetic Biology in Human Stem Cells
NSF · $462k · 2014–2021
Assembly of Novel Gene Editing Particles to Understand Genome Surgery in Patient-Derived Cells
NIH · $3.6M · 2016–2026
EAGER BIOMANUFACTURING: A Microscale Testbed to Assay and Manufacture CAR T-Cell Immunotherapies
NSF · $300k · 2016–2020
Frequent coauthors
- 85 shared
Melissa C. Skala
Morgridge Institute for Research
- 69 shared
Amr A. Abdeen
University of Wisconsin–Madison
- 68 shared
Christian M. Capitini
University of Wisconsin–Madison
- 67 shared
Katherine P. Mueller
University of Pennsylvania
- 54 shared
Jared Carlson-Stevermer
Synthego (United States)
- 52 shared
Benjamin Steyer
Smith-Kettlewell Eye Research Institute
- 51 shared
Bikash R. Pattnaik
University of Wisconsin–Madison
- 51 shared
Shaoqin Gong
Awards & honors
- STAT, STAT “Who to Know” in Therapeutic Gene Editing (2024)
- National Academy of Medicine, Emerging Leaders in Health and…
- Wisconsin Alumni Research Foundation (WARF), H. I. Romnes Fa…
- American Institute for Medical and Biological Engineering (A…
- Retina Research Foundation, Kathryn and Latimer Murfee Chair…
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