Jyoti Jaiswal Jyoti Jaiswal
Professor of Genomics and Precision Medicine
Professor of Pediatrics (Secondary)

Office Phone: 202-476-6029
Email: Email
Department: Genomics and Precision Medicine


As a cell biologist, Jyoti studied regulation of cell fate determination for his graduate work and helped develop microscopy tools for live imaging in his postdoctoral studies at the Rockefeller University. His laboratory at the Children’s National Research Institute uses these tools to study intracellular trafficking machinery and its role in diseases. He is involved in broader use of optical imaging and other approaches to study biology at single cell level and is passionate about training the next generation of biomedical researchers.


Our studies examine basic cell biology of injury and infection with an emphasis of translating our findings to diseases linked to these cellular processes. The limiting membrane around the protoplasm called the plasma membrane created the building block of life – ‘The Cell’. Cells use various mechanisms to maintain the integrity of their plasma membrane in the face of chemical, mechanical or pathogen-induced damage. Failure to repair this damage is lethal for the cell and compromises tissue function. The molecular and cellular processes that help cells cope with injury, are activated in response to injury and infections, and compromised in many genetic diseases. We study these processes and diseases to both understand and to develop treatments for such diseases.

Mitochondria as a local signaling hub

A serendipitous discovery that mitochondrial proteins accumulate at the injured cell membrane and mitochondria in muscle fiber can accumulate at the site of injury, led us to studies that have uncovered the requirement of mitochondria in repairing cell membrane injury. We find that calcium that enters the injured cell is taken up by mitochondria in a regulated manner, which allows controlled production of reactive oxygen species (ROS). This ROS locally activates the reorganization of actin cytoskeleton to enable closure of the cellular wound. Despite being organized in a cell-wide network, mitochondria can act locally by controlled mitochondrial fission at the site of injury. We study how mutations that alter mitochondrial calcium uptake, ROS production or fission compromise cell repair and lead to muscle diseases. Injury-mediated regulation of these processes in healthy cells, their downstream effectors, and the role of mitochondrial interactions with other organelles in controlling this repair mechanism are some of the other open questions.

Further reading

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949579/
  2. https://www.nature.com/articles/cdd2016127
  3. https://www.jbc.org/content/287/36/30455.full.pdf
  4. https://rupress.org/jcb/article/219/5/e201909154/151605

Membrane trafficking in cell repair

Our studies are uncovering the role of several cellular compartments, calcium binding proteins, and lipids in cell repair. These include the role of lysosomes, which are the major calcium-triggered secretory compartments in mammalian cells. Defect in fusion of lysosomes impairs release of the lipid modifying lysosomal enzyme, Acid Sphingomyelinase (ASM), and results in diseases such as dysferlinopathy or Limb Girdle Muscular Dystrophy 2B (LGMD2B). Fusion of lysosomes and other calcium-regulated organelles in cells is controlled by multiple calcium binding proteins, including annexins, dysferlin, and synaptotagmins, that we have examined for their role in calcium-triggered vesicle fusion during cell repair. Our work has also identified the need for the cytosol and endoplasmic reticulum to buffer injury-triggered calcium increase, to control cell repair. A deficit in this process contributes to Limb Girdle Muscular Dystrophy 2B (LGMD2L). Additionally, we find that beyond triggering membrane fusion, calcium also triggers membrane scission by the ESCRT (endosomal sorting complex required for transport) machinery, which is required for cell repair. This is regulated by the calcium brining protein - ALG-2 (Apoptosis linked gene-2), to direct scission and shedding of the damaged parts of the plasma membrane to help close a wound. We are continuing to study additional regulators of calcium-dependent membrane trafficking and their role in cell repair.

Further reading

  1. https://www.nature.com/articles/cddis2014272/
  2. https://www.nature.com/articles/s41420-019-0197-z
  3. https://www.nature.com/articles/cdd2015124
  4. https://www.nature.com/articles/ncomms6646/

Mesenchymal stem cells and muscle repair

While skeletal muscle primarily consists of syncytial cells called myofibers, interactions between several muscle-resident mononucleated cell types enable skeletal muscle maintenance and repair. Mesenchymal stem cells called ‘fibroadipogenic progenitors’ (FAPs) constitute one such cell type. FAPs enable homeostatic maintenance of skeletal muscle and are required for muscle repair. However, dysregulation of FAP leads to failed repair and degeneration of muscles in multiple muscular dystrophies. Using models for LGMD2B and Duchenne muscular dystrophy (DMD), we find that extracellular signaling by proteins including Annexin A2 and TGFβ cause the FAPs to accumulate and undergo osteogenic, fibrotic, or adipogenic differentiation in a disease-specific manner. We are examining how FAPs facilitate repair of healthy muscles, and how altered extracellular environment in diseased muscle alters proliferation and differentiation FAPs, inhibits myogenesis, and contributes to the progressive muscle loss that marks these diseases.

Further reading

  1. https://www.nature.com/articles/s41467-019-10438-z
  2. https://insight.jci.org/articles/view/135703
  3. https://www.frontiersin.org/articles/10.3389/fphys.2019.00828/full

Therapies to treat muscular dystrophies

Several genetic and metabolic diseases interfere with the efficient repair capacity of the muscle, leading to debilitating neuromuscular diseases. These include Limb Girdle Muscular dystrophies, Duchenne Muscular dystrophy, and multiple myopathies. Extending our basic discoveries, we are involved in developing and testing drugs to treat diseases involving muscle injury and degeneration. These studies contributed to the development of ‘Vamorolone’ a modified steroid analog that efficiently stabilizes cell membranes, reducing their susceptibility to injury and improving their ability to repair. It is also a potent anti-inflammatory agent, which helps reduce chronic inflammation of diseased muscles. This drug has shown safety and efficacy in preclinical studies for LGMD2B and in human trials for DMD. In an alternate approach, we are employing Adeno Associated Virus (AAV) vector for a gene therapy approach to address reduced ASM secretion by LGMD2B muscle. In another collaborative gene therapy approach we are working to enhance the efficacy of antisense oligonucleotide-based drug delivery for treating DMD. We are also testing drugs that target FAPs to reduce muscle loss in muscular dystrophies. Another collaborative study established the benefit of low intensity exercise to address symptoms and muscle damage in myositis patients by improving mitochondrial function. These multi-pronged studies are beginning to translate our discoveries to target muscle diseases that result from poor repair of injured muscle cells or tissues.

Further reading

  1. https://www.sciencedirect.com/science/article/pii/S152500161830368X
  2. https://www.embopress.org/doi/full/10.1002/emmm.201302621
  3. https://www.nature.com/articles/s41467-017-00924-7
  4. https://onlinelibrary.wiley.com/doi/abs/10.1002/path.5309

Host-pathogen interactions during viral infection

Viruses tap into the inner workings of the cell to support their own proliferation and spread, revealing many hidden workings of the cell. Aside from giving insights into cellular machinery, an understanding of these mechanisms can guide safe antiviral therapies. Through collaborations withs virologists and clinicians, we study host-cell interactions with viruses including Human Cytomegalovirus (HCMV), Human Immunodeficiency Virus (HIV), Respiratory Syncytial Virus (RSV), and most recently SARS-CoV-2. These studies have led to insights into viral entry and virus-mediated subversion of ER-mitochondria contacts. Beyond their effect on cells, viruses such as RSV and SARS-Cov-2 also subvert the immune response to support their entry and prevent clearance by the immune system. We are studying the systemic responses by the airway epithelium to these respiratory viruses and how genetic and other factors disrupt these responses.

Further reading

  1. https://www.atsjournals.org/doi/10.1165/rcmb.2020-0352LE
  2. https://www.nature.com/articles/s41598-017-00039-5
  3. https://www.mdpi.com/1999-4915/6/4/1612/htm
  4. https://jasn.asnjournals.org/content/jnephrol/28/3/862.full.pdf

Complete list of publications: https://scholar.google.com/citations?user=asYBs1gAAAAJ&hl=en&oi=ao


Chandra G, Sreetama SC, Mazala D, Charton K, vanderMeulen JH, Richard I, Jaiswal JK. Endoplasmic reticulum maintains ion homeostasis required for plasma membrane repair. J Cell Biology. 2021; 220:doi: 10.1083/jcb.201909154.

Horn A, Raavicharla S, Shah S, Cox D, Jaiswal JK. Mitochondrial fragmentation enables localized signaling required for cell repair. J Cell Biology. 2020;219(5):e201909154. doi: 10.1083/jcb.201909154.

Mázala DA, Novak JS, Hogarth MW, Nearing M, Adusumalli P, Tully CB, Habib NF, Gordish-Dressman H, Chen YW, Jaiswal JK, Partridge TA. TGF-beta-driven muscle degeneration and failed regeneration underlie disease onset in DMD mouse model. JCI Insight; 2020;5(6): e135703. doi: 10.1172/jci.insight.135703.

Hogarth MW, Defour A, Lazarski C, Gallardo E, Diaz Manera J, Partridge TA, Nagaraju K, Jaiswal JK. Fibroadipogenic progenitors are responsible for muscle loss in limb girdle muscular dystrophy 2B. Nature Communications. 2019;10(1):2430. doi: 10.1038/s41467-019-10438-z.

Sreetama SC, Chandra G, Van der Meulen JH, Ahmad MM, Suzuki P, Bhuvanendran S, Nagaraju K, Hoffman EP, Jaiswal JK. Membrane Stabilization by Modified Steroid Offers a Potential Therapy for Muscular Dystrophy Due to Dysferlin Deficit. Molecular Therapy 2018 Sep 5;26(9):2231-2242. doi: 10.1016/j.ymthe.2018.07.021.

Horn A, Van der Meulen JH, Defour A, Hogarth M, Sreetama SC, Reed A, Scheffer L, Chandel NS, Jaiswal JK. Mitochondrial redox signaling enables repair of injured skeletal muscle cells. Science Signaling. 2017;10(495):eaaj1978. doi: 10.1126/scisignal.aaj1978.

Vila MC, Rayavarapu S, Hogarth MW, Van der Meulen JH, Horn A, Defour A, Takeda S, Brown KJ, Hathout Y, Nagaraju K, and Jaiswal JK (2017) Mitochondria mediate cell membrane repair and contribute to Duchenne muscular dystrophy. Cell Death and Differentiation. 24:330-342.

Jaiswal JK, Lauritzen SP, Scheffer L, Sakaguchi M, Bunkenborg J, Simon SM, Kallunki T, Jaattela M and Nylandsted J S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nature Communications. 2014;5:3795; PMC4026250

Scheffer LL, Sreetama SC, Sharma N, Medikayala S, Brown KJ, Defour A, Jaiswal JK. Mechanism of Ca²?-triggered ESCRT assembly and regulation of cell membrane repair. Nature Communications. 2014;5:5646. doi: 10.1038/ncomms6646.

Jaiswal JK, Rivera VM, Simon SM. Exocytosis of post-Golgi vesicles is regulated by components of the endocytic machinery. Cell. 2009;137(7):1308-19. doi: 10.1016/j.cell.2009.04.064.

Industry Relationships and Collaborations

This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.

  • None