Hiranmoy Das, PhD, currently a Professor in the Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas, USA. Dr. Das earned his BS (Hons), MS, and Ph.D. from Calcutta University, West Bengal, India. He received his postdoctoral training from Hyogo Adult Medical Center, Hyogo, Japan, and from the Department of Internal Medicine at Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. Prior to his arrival at TTUHSC in Amarillo, Dr. Das served as an Associate Professor for the Department of Internal Medicine at The Ohio State University, as an Assistant Professor for the Case Western Reserve University’s Cardiovascular Research Institute in Cleveland, and as an Instructor in Medicine for Harvard Medical School, Boston, MA. Dr. Das’ current research focuses on isolating and expanding a variety of human adult stem cells and using them for the treatment of various degenerative diseases in preclinical models, like hind limb ischemia, myocardial ischemia, osteoporosis and wound healing. Dr. Das also utilizes human immune cells, specifically, gamma delta T-cells in immunotherapy, for treating various cancers (breast, ovary and others) using preclinical models. In addition, he investigates the role of transcriptional factor KLF2 in regulating immune cells, specifically monocytes, in rheumatoid arthritis and inflammation. Dr. Das also serves as a member of the editorial board for several peer-reviewed journals and serves on the grant review panels of various state, national and international funding agencies.
1. Stem cell therapy using autologous stem cells to treat degenerative diseases has been promising, however the limited availability and compromised quality of progenitor cells in aged and diseased patients limit its therapeutic potential. Alternatively, use of cord blood-derived stem cells is advantageous as it is easy to harvest, harmless to donor, ethical, ontogenetically primitive and can be stored in cord blood bank for years. Moreover, cord blood-derived stem cell transplantation is associated with reduced risk of developing graft versus host disease. Nevertheless, small number of stem cells provided by a single cord limits its clinical application. Our laboratory has developed a nanofiber-based ex-vivo human umbilical cord blood-derived stem cell expansion technology, which not only preserves stem cell phenotype, but also provides required number of biologically functional stem cells. Furthermore, we can genetically modify nanofiber-expanded stem cells to enhance their angiogenic and therapeutic potential for various degenerative diseases such as hind limb ischemia, myocardial ischemia, stroke-mediated ischemia, wound healing and osteoporosis. Current investigations use immunocompromised murine, rat and swine models for relevant studies. Molecular aspects of stem cell functionality are also being investigated in these animal models after cell-based therapy.2. The molecular mechanisms regulating activation and functionality of monocytes remain incompletely understood in the context of inflammation. We provided evidence that a transcription factor, Kruppel-like factor 2 (KLF2), inhibits proinflammatory activation of monocytes. KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease (CAD). KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis in vitro. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, we show that KLF2 inhibits the transcriptional activity of both NF-kB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. Current investigations focus on the role of KLF2 in the genetically altered murine model of rheumatoid arthritis.3. Human gamma delta (γδ) T cells represent a small subset of T cell population that possesses distinct T cell receptor (TCR) on their surface. Majority of γδ T cells are Vγ2Vδ2 subset. This subset can increase 2- to 10-fold in peripheral blood in a variety of infectious diseases. Vγ2Vδ2 T cells may be considered part of the adaptive immune system as they have a memory phenotype, junctionally diverse TCR’s that require gene rearrangement for their cell surface expression and the ability to undergo either anergy or expansion depending on the availability of co-stimulation. On the other hand, Vγ2Vδ2 T cells are also considered a part of the innate immune response. Pattern recognition by the Vγ2Vδ2 TCR allows the expansion of memory γδ T cells into a large numbers in normal adults during microbial infections. These large numbers of memory T cells are capable of responding to antigens produced by microbes and thus may bridge the gap between the innate and adaptive immune responses. MHC class I chain related molecules A and B (MICA and MICB, danger signals), which are widely expressed in epithelial tumor cells, and virally or bacterially infected cells, can be recognized by γδ T cells and NK cells via NKG2D; a signaling pathway responsible for enhanced cytotoxicity against infected or tumor cells. Our current focus is to identify molecules responsible for recognition of various tumor cells (such as ovarian, breast, and cervical) by γδ T cells. The ultimate goal is to develop combined targeted immunotherapy with γδ T cells for various tumors.