Research

Team MISTRI aspires to develop cellular immunotherapy products against cancer; drug formulations for efficient diabetic wound healing; repurposing and development of novel drugs to induce antimicrobial peptides by innate immune cells against multi-drug resistant bacterial infections; improving oral health through better dental drafts and implants; hormone-free therapy for infertility and contraception. We aim to modulate ion channel signalling towards metabolic rewiring of cells to improve their function in pathological states. We employ high resolution and live-cell microscopy, flow cytometry, biochemical assays and in vivo mice experimentation together with clinical samples in our studies.

We are actively looking for multidisciplinary Collaborators, Students, Postdocs, Industrial partners and Philanthropists to assist us in delivering novel, effective and affordable therapies to the clinics.

MISTRI

Tissue Restoration Lab (TRL) is dedicated to develop novel therapeutic technologies by “Harnessing the therapeutic potential of ion channels” in immune cells.
We call ourselves “Team MISTRI” , where we aim at Modulating Ion channels for Superior Tissue Restoration via Immune regulation.
At the Basic biology level, we are interested to understand the (patho)physiological role of lysosomal, mitochondrial and plasma membrane-bound ion channels in immune cells like Natural Killer (NK) cells, T cells, Macrophages and Keratinocytes utilizing high resolution microscopy, multi-colour flow cytometry and biochemical analysis.
At the Clinical level, we are interested to understand the role of these ion channels in solid and haematological cancer, diabetic wound healing, oral health and reproduction with the support of our clinical collaborators.
At the Translational level, we are focussed on developing novel cellular immunotherapy products, drugs, nano-formulations, drug-releasing hydrogels, 3-D scaffolds with the support of our chemistry and biomaterials collaborators.

MISTRI

INFINITY

Altered behavior of immune cells impairs our ability to control diseases like cancer and infections.
We are developing basic biological understanding on the role of ion channels in immune cells with or without infection. Our main focus is to target the ion channels present in Lysosome or Mitochondria, to be able to metabolically rewire the immune cells for better activity.
Primary NK, T cell, Macrophages derived from human blood, murine spleen or bone marrow will be subjected to microscopy, flowcytometry and biochemical assays to understand the extent to which mitochondrial and lysosomal ion channels can modulate the physiology and activity of the immune cells.

Ion channels in Infection and Immunity (INFINITY)

INFINITY

Tailoring Anti-Cancer Therapy via Immunomodulatory Channels (TACTIC)

TACTIC

Engineered NK cells and immunomodulators for CD8+ T cells can be the most affordable and highly effective anti-cancer immunotherapy, with minimal side-effects. NK cells and CD8+ T cells have the unique specificity of detecting and attacking only the cancer cells, by detecting the absence of MHC-I and presence of stress-associated ligands.
However, the efficacy of cytotoxic cells is diminished as their metabolism is altered in the tumor microenvironment, like hypoxia, low nutrients and altered extracellular matrix.
NK cells will be isolated, enriched or designed, by inducing metabolic rewiring via ion channels and educating KIRs for better anti-tumor activity. Further, we will explore the use of pharmacological modulators, genetic manipulation, and humanized antibodies to improve immune function.
Special emphasis will be on immunologically cold tumors like prostate cancer, oral cancer, sarcomas, which suppress their inflammatory molecule secretion to avoid attracting immune cell infiltration.

TACTIC

IMPACT

We are using wound healing as a model system to establish the practical implications of modulating the ion channels of the immune cells.
WT and db/db mice will be utilized for in vivo studies, while ex vivo assays will be performed using human skin punch biopsies.
Ion channels regulate the ability of immune cells to sense, respond and transform at wound sites. However, we still have limited insights into how these channels contribute to wound healing, especially in diabetes. The role of these channels in supporting proliferation, migration, epithelial barrier integrity maintenance is being evaluated by us.
Impact of ion channels on production of antimicrobial peptides by keratinocytes, will be examined under normoglycemic and hyperglycemic conditions. The migration, differentiation and contribution of other immune cells like macrophages in diabetic wound healing is being evaluated.
Moreover, S. aureus and Group A streptococcus strains isolated from wounds will be used in wound infection models, both under diabetic and non-diabetic conditions. Critical findings will be confirmed using human skin biopsies ex vivo with and without infection.

Investigating Modulation of Pressure Activated Channels for Tissue Restoration (IMPACT)

IMPACT

Ion channels in Fertility and Contraception (FRICTION)

FRICTION

The ion channels guide the sperm during its movement in the female reproductive tract. Since mitochondria have a vital role in spermatogenesis, sperm motility and ROS production, understanding the role of mitochondrial ion channels will be helpful in improving fertility.
In future, we aim to minimize severe side effects associated with hormonal interventions for reproduction. FRICTION aspires to integrate pharmacological modulation of ion channels and sorting highly thermo-responsive sperm to improve male fertility and contraception outcomes.

FRICTION

SHANTI

We have identified ion channels that regulate osteogenesis, osteoclastogenesis, wound healing, vascularization, inflammation. We aim to prepare hydrogels for slow, sustained release of ion channel modulators which can serve as improved bone grafting materials.
Further, we are also developing drug eluting hydrogel or nanoparticle coated dental implants for better osseointegration.
Together with our biomaterials collaborators, we are making nanoformulations and liposomes for improved and on-target delivery of ion channel modulators to the pathological sites, like the plaque sites in atherosclerosis.
We are also working on drug eluting biomaterials for use against MDR bacteria causing periodontitis and gingivitis, or in case of implant failure, oral reconstructive surgeries.