Honors & Awards
Best Oral Presentation Award, Biomaterials day, Society for Biomaterials (Jun 2014)
BMES Student Travel Award, Biomedical Engineering Society (Oct 2014)
ATVB Young Investigator Travel Award, American Heart Association (Nov 2014)
Kuhn Intellectual Entrepreneurship Award, UT Austin (Aug 2015)
Publons Top Peer Reviewer Award, Publons (Sep 2017)
Boards, Advisory Committees, Professional Organizations
Technology Representative, Protein and Cell Interactions Special Interest Group (PCI-SIG), Society for Biomaterials (2015 - 2017)
Treasurer, Berkeley Postdoctoral Association (2016 - 2017)
Secretary and Treasurer, Cardiovascular Biomaterials Special Interest Group (CVB-SIG), Society for Biomaterials (2017 - Present)
Editorial Board Member, Journal of Postdoctoral Research (2017 - Present)
Editorial Board Member, Frontiers in Molecular Biosciences (2017 - Present)
Editorial Board Member, Frontiers in Materials (2017 - Present)
Editorial Board Member, Frontiers in Biotechnology and Bioengineering (2017 - Present)
Editorial Board Member, Scientific Reports (2017 - Present)
Bachelor of Technology, Indian Institute of Technology, Kharagpur (2010)
Master of Science in Engr, University of Texas Austin (2013)
Doctor of Philosophy, University of Texas Austin, Biomedical Engineering (2014)
Subhamoy Das and Aaron B. Baker. "United States Patent USPTO 6794 BAK- New provisional; 10046-107PV1 Syndecan-4 proteoliposomes for enhanced cutaneous wound healing and minimized inflammatory immune response.", University of Texas, Austin
Current Research and Scholarly Interests
Enteric Nervous System
Syndecan-4 enhances PDGF-BB activity in diabetic wound healing
2016; 42: 56-65
Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan-4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds.Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is currently the only approved growth factor for enhancing wound healing. However, it has not seen widespread adoption due to limited efficacy and high cost. In this work, we have developed an enhancing agent that improves the activity of PDGF-BB in promoting wound healing in animals with diabetes. This co-therapy may be useful in improving the efficacy of PDGFBB and enhance its safety through lowering the dose of growth factor needed to improve wound healing.
View details for DOI 10.1016/j.actbio.2016.07.001
View details for Web of Science ID 000383292700005
View details for PubMedID 27381525
Syndesome Therapeutics for Enhancing Diabetic Wound Healing
ADVANCED HEALTHCARE MATERIALS
2016; 5 (17): 2248-2260
Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenges in designing treatments that are effective in long-standing, nonhealing wounds. Here, an optimized wound healing gel was developed that delivers syndecan-4 proteoliposomes ("syndesomes") with fibroblast growth factor-2 (FGF-2) to enhance diabetic wound healing. In vitro studies demonstrate that syndesomes markedly increase migration of keratinocytes and fibroblasts isolated from both nondiabetic and diabetic donors. In addition, syndesome treatment leads to increased endocytic processing of FGF-2 that includes enhanced recycling of FGF-2 to the cell surface after uptake. The optimized syndesome formulation was incorporated into an alginate wound dressing and tested in a splinted wound model in diabetic, ob/ob mice. It was found that wounds treated with syndesomes and FGF-2 have markedly enhanced wound closure in comparison to wounds treated with only FGF-2. Moreover, syndesomes have an immunomodulatory effect on wound macrophages, leading to a shift toward the M2 macrophage phenotype and alterations in the wound cytokine profile. Together, these studies show that delivery of exogenous syndecan-4 is an effective method for enhancing wound healing in the long-term diabetic diseased state.
View details for DOI 10.1002/adhm.201600285
View details for Web of Science ID 000383776300011
View details for PubMedID 27385307
View details for PubMedCentralID PMC5228475
Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes
ADVANCED HEALTHCARE MATERIALS
2016; 5 (9): 1008-1013
Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype.
View details for DOI 10.1002/adhm.201500993
View details for Web of Science ID 000377528000003
View details for PubMedID 26891081
View details for PubMedCentralID PMC4864113
Overcoming disease-induced growth factor resistance in therapeutic angiogenesis using recombinant co-receptors delivered by a liposomal system
2014; 35 (1): 196-205
Current treatment options for ischemia include percutaneous interventions, surgical bypass or pharmacological interventions aimed at slowing the progression of vascular disease. Unfortunately, while each of these treatment modalities provides some benefit for patients in the short-term, many patients have resistant or recurrent disease that is poorly managed by these therapies. A highly appealing strategy for treating ischemic disease is to stimulate the revascularization of the tissue to restore blood flow. While many techniques have been explored in this regard, clinically effective angiogenic therapies remain elusive. Here, we hypothesized that the presence of co-morbid disease states inherently alters the ability of the body to respond to angiogenic therapies. Using a mouse model of diabetes and obesity, we examined alterations in the major components for the signaling pathways for FGF-2, VEGF-A and PDGF under normal and high fat dietary conditions. In skeletal muscle, a high fat diet increased levels of growth factor receptors and co-receptors including syndecan-1, syndecan-4 and PDGFR-α in wild-type mice. These increases did not occur in Ob/Ob mice on a high fat diet and there was a significant decrease in protein levels for neuropilin-1 and heparanase in these mice. With the aim of increasing growth factor effectiveness in the context of disease, we examined whether local treatment with alginate gel-delivered FGF-2 and syndecan-4 proteoliposomes could overcome the growth factor resistance in these mice. This treatment enhanced the formation of new blood vessels in Ob/Ob mice by 6 fold in comparison to FGF-2 delivered alone. Our studies support that disease states cause a profound shift in growth factor signaling pathways and that co-receptor-based therapies have potential to overcome growth factor resistance in the context of disease.
View details for DOI 10.1016/j.biomaterials.2013.09.105
View details for Web of Science ID 000328006100019
View details for PubMedID 24138828
View details for PubMedCentralID PMC3909708
Thiophene bridged hydrocyanine - a new fluorogenic ROS probe.
Chemical communications (Cambridge, England)
2017; 53 (73): 10184–87
Hydrocyanines are a class of commonly used reactive oxygen species (ROS) fluorescent imaging probes, which can image ROS in cell culture, organ culture, and in vivo. However, despite their widespread use, hydrocyanines have several drawbacks that limit their effectiveness, such as a high rate of auto-oxidation, a small Stokes shift, and poor water solubility. In addition, the hydrocyanines oxidize into cyanine dyes, which themselves decompose in the presence of ROS, and this further lowers their sensitivity towards detecting ROS. In this report, we present a new hydrocyanine analog, termed as thiophene-bridged hydrocyanine (TBHC), which has its double bonds replaced with a bisthiophene. TBHC is 8.06-fold more stable to auto-oxidation than the hydrocyanine hydro-Cy5 and is significantly better at imaging ROS in cell culture.
View details for DOI 10.1039/c7cc04847e
View details for PubMedID 28853453
Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis
2016; 94: 45-56
Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these treatments often have long term disease states and co-morbidities, such as diabetes and obesity, that make them resistant to angiogenic stimuli. In this study, we identified that human patients with type 2 diabetes have reduced levels of glypican-1 in the blood vessels of their skin. The lack of this key co-receptor in the tissue may make the application of exogenous angiogenic growth factors or cell therapies ineffective. We created a novel therapeutic enhancer for growth factor activity consisting of glypican-1 delivered in a nanoliposomal carrier (a "glypisome"). Here, we demonstrate that glypisomes enhance FGF-2 mediated endothelial cell proliferation, migration and tube formation. In addition, glypisomes enhance FGF-2 trafficking by increasing both uptake and endosomal processing. We encapsulated FGF-2 or FGF-2 with glypisomes in alginate beads and used these to deliver localized growth factor therapy in a murine hind limb ischemia model. Co-delivery of glypisomes with FGF-2 markedly increased the recovery of perfusion and vessel formation in ischemic hind limbs of wild type and diabetic mice in comparison to mice treated with FGF-2 alone. Together, our findings support that glypisomes are effective means for enhancing growth factor activity and may improve the response to local angiogenic growth factor therapies for ischemia.
View details for DOI 10.1016/j.biomaterials.2016.03.048
View details for Web of Science ID 000376211800005
View details for PubMedID 27101205
Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing.
Frontiers in bioengineering and biotechnology
2016; 4: 82-?
Wound healing is an intricate process that requires complex coordination between many cell types and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care, the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds, including excessive inflammation, ischemia, scarring, and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or are currently used in clinical practice.
View details for PubMedID 27843895
View details for PubMedCentralID PMC5087310
Nanoscale Strategies: Treatment for Peripheral Vascular Disease and Critical Limb Ischemia
2015; 9 (4): 3436-3452
Peripheral vascular disease (PVD) is one of the most prevalent vascular diseases in the U.S. afflicting an estimated 8 million people. Obstruction of peripheral arteries leads to insufficient nutrients and oxygen supply to extremities, which, if not treated properly, can potentially give rise to a severe condition called critical limb ischemia (CLI). CLI is associated with extremely high morbidities and mortalities. Conventional treatments such as angioplasty, atherectomy, stent implantation and bypass surgery have achieved some success in treating localized macrovascular disease but are limited by their invasiveness. An emerging alternative is the use of growth factor (delivered as genes or proteins) and cell therapy for PVD treatment. By delivering growth factors or cells to the ischemic tissue, one can stimulate the regeneration of functional vasculature network locally, re-perfuse the ischemic tissue, and thus salvage the limb. Here we review recent advance in nanomaterials, and discuss how their application can improve and facilitate growth factor or cell therapies. Specifically, nanoparticles (NPs) can serve as drug carrier and target to ischemic tissues and achieve localized and sustained release of pro-angiogenic proteins. As nonviral vectors, NPs can greatly enhance the transfection of target cells with pro-angiogenic genes with relatively fewer safety concern. Further, NPs may also be used in combination with cell therapy to enhance cell retention, cell survival and secretion of angiogenic factors. Lastly, nano/micro fibrous vascular grafts can be engineered to better mimic the structure and composition of native vessels, and hopefully overcome many complications/limitations associated with conventional synthetic grafts.
View details for DOI 10.1021/nn507269g
View details for Web of Science ID 000353867000008
View details for PubMedID 25844518