I will review the history and potential of biotechnology, and why diversity is integral.

Preeclampsia (PE) impacts around 2-8% of all pregnancies globally each year, accounting for 70,000 maternal and 500,000 fetal deaths (Rana et al. 2019). Failed transformation of the maternal spiral artery into a low resistance conduit and sustained placental hypoxia are widely accepted as initiating events for PE. Placental adaptations, specifically at the maternal-fetal interface in chorionic villi, however, are not well-understood and likely fuel PE. Moreover, pericyte (PC) recruitment to microvessels involves platelet-derived growth factor (PDGF)-BB signaling, though little is known about contributions of a soluble isoform of PDGF Receptor-beta (sRβ) recently identified by our lab and others (Payne et al. 2023). Here, we characterized early vessel formation within in vivo and in vitro models for follow-on mechanistic experiments aimed at identifying the role of sRβ in pericyte investment. From embryonic day 9.5 (E9.5) to E18.5, we found that signatures of murine placenta endothelial cells (ECs) increased, while PC presence and Type IV Collagen deposition was maintained along placental capillaries. Transcripts of Pdgfbb and full-length Pdgfrb steadily increased, while sRβ mRNA remained relatively constant, though sRβ protein decreased from E14.5 to E18.5. These results suggest that these components regulating the PDGF-BB pathway are promoting PC recruitment to placental capillaries as these vessel networks expand. These data align with increased PC precursors seen in our in vitro model exposed to EC growth media. Follow-up studies using in vivo and in vitro models are ongoing to (i) pinpoint the cellular sources for these regulators, and (ii) establish how they are functionally related.

Ambient air pollution is associated with an increasing number of diseases, including premature death caused by heart disease, stroke, chronic obstructive pulmonary disease (COPD) and lung cancer. However, the underlying mechanisms leading to detrimental effects on health by air pollution is yet to be understood. This has made it difficult the development of sensitive and specific biomarkers that, at the molecular level, can report cellular toxicity upon exposure to various air chemicals. We have developed new models, based on prominent RNA marks to uncover specific patterns of oxidation induced by various specific air pollution mixtures in healthy epithelial lung cells that could be used as sensitive and early indicators of air-induced cell toxicity. Taken together, our study features the strength of mechanistic characterizations to facilitate the discovery of underling processes that are not well described at the molecular level by current approaches to understand air pollution and its disparities. Thus, this presentation will focus on the ways that this research has informed the relationship between the atmospheric agents and molecular cellular responses implicated with diseases. We will discuss our findings uncovering approaches to evaluate cellular susceptibility to air pollution mixtures and the impact of these on overall cell function. 

The discovery of immune therapies to eradicate cancer was a remarkable breakthrough in science and was awarded the Nobel Prize in 2018. Unfortunately, immune therapies still fail in colorectal cancer, the incidence of which is rising at alarming rates. Colorectal cancer, a cancer of the intestinal epithelium, to understand how to design new therapies, we must understand how cancer-causing experiences alter immune dynamics within the intestinal epithelial layer. We focus on the behaviors of intra-epithelial gamma delta T cells (gdT), which are abundant in both healthy intestinal epithelium and colon tumors. gdT cells are IFNg-producing and IL-17-producing, and while the IFNg-producing subset is abundant in the healthy epithelium, colon tumors are instead enriched in IL-17-producing gdT cells (gd17), which are thought to promote tumorigenesis. The origins of tumor-promoting gd17 cells are unknown since they are absent in healthy epithelium. Here we found that colon inflammation, the highest risk factor for colorectal cancer, results in migration of gd17 cells to the intestinal epithelium. Investigation of the signals driving this migration revealed a role for both T cell receptor signals and intestinal microbiota in gd17 activations and movement into the epithelial layer. We additionally found that IL-17 production by gd17 cells in the epithelial layer is regulated by PD-1, a receptor known for its roles in tumor immunotherapy. These results suggest that environmental insults linked to colorectal cancer activate and modulate the behavior and localization of IL-17-producing gd17 cells. Therapies targeting these responses of gd17 cells hold promise for treating colorectal cancer.

A Vest all-in-one Health Monitoring system with real time monitoring and user interface to monitor and communicate body’s vital information like ECG, Body Temperature, SPO2, Blood Pressure, etc. which is critically needed to analyse the body situation working in a harsh and rugged environment like Oil & Gas Industry, Aerospace, Security and Defence, Health and Safety and having self recharging capability by a human body temperature using seebeck principle to get required power for bio sensors. V-HMS-FTM (Vest Health monitoring System Based on Flexible Thermoelectric Module) is a module which works on utilizing body heat to convert into electricity using See beck principle i.e. if there is a sufficient temperature difference between the materials (PN Junction diode) EMF would be generated across the terminals. Our Objective is to develop a flexible thermoelectric material which can easily attach to any existing fabric and using flexible electronic we can capture a body heat in any situation from -40 degree to +60 Degree of locations. The required voltage output is useful for biosensors, other electric stuff for physiological monitoring. Single integrated Vest health monitoring system Bluetooth connectivity, family group sharing. Real time monitoring on mobile app. Customizable as per industry requirements. Washable, quick dry flexible fabric. Routine body check-up to identify possible deviations from the normal health. Breathable, lightweight, anti-odor, chlorine resistant, UV protection. Data interpretation and analysis module storage capability. Virtual Hospital, Telemedicine can be possible with V-HMS. Works on flexible TEG utilizing body heat and no sweating.

The Ebong research laboratory investigates how mechanical forces influence endothelial cells, which line the blood vessels and protect them from diseases such as atherosclerosis and cancer metastasis. A primary focus is on studying the structure and function of the endothelial cell glycocalyx, which acts as a node that receives signals from the extracellular environment and transmits them into the endothelial cells. The endothelial cell glycocalyx has a gel-like structure, composed of sugar molecules and proteins. One of its primary functions is to convert mechanical forces from the surrounding environment into biochemical responses within the endothelial cells, helping to protect blood vessels from endothelial cell-dependent diseases. In this way, the glycocalyx provides fragile blood vessels with the resilience needed to withstand the mechanical forces exerted within and upon them. Unfortunately, the glycocalyx sheds in the presence of disease, particularly at blood vessel branch points, where fluid dynamics are unsteady and commonly co-localized with atherosclerotic plaques. Recent findings also suggest that excessive tissue stiffness adversely affects the glycocalyx. As a result, it is of significant interest to study how gradual degradation or unfavorable changes in the glycocalyx initiate or promote pathological processes that lead to the formation of atherosclerotic lesions or secondary cancers. The Ebong laboratory creates experimental systems that combine fluids, mechanically tunable substrates, and mammalian endothelial cells to replicate both healthy and disruptive mechanobiological conditions. This approach uncovers the complexities of the relationship between mechanical forces, the glycocalyx, and endothelial cells. These findings are further validated by live animal studies, which assess how the results translate to real disease conditions. The long-term goal is to apply insights from mechanobiology, endothelial cell function, and glycocalyx structure to develop clinically relevant therapies that can reverse disease progression.

Advances in electronic design automation (EDA) have played a pivotal role in the evolution of complex electronic systems. The capability to independently specify, design, and assemble these systems across various abstraction levels has spurred significant growth in the semiconductor industry. Engineered, living biological systems that can make decisions, process information, record events, adapt to specific inputs and outputs, and communicate with one another are poised to deliver groundbreaking solutions in bio-therapeutics, bio-materials, bio-energy, and bio-remediation. I will explore how traditional logic synthesis techniques can be leveraged to create genetic circuits for synthetic biology. These living circuits can be combined with the parallel design of cost-effective, fully customized microfluidics to form "hybrid bio-electronic systems." Specifically, I will discuss how CAD tools, software systems, and low-cost manufacturing methods can enable dynamically programmable microfluidics for synthetic biological communication and memory systems. I will conclude with insights on how these approaches can be utilized in commercial endeavors as well as community-driven open-source software initiatives.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease classified as an autoimmune disorder due to the immune system's aggression towards rheumatic antigens and the presence of autoantibodies. Although the origins of RA remain unclear, its prevalence is often linked to genetic and environmental factors. Current treatments typically involve biologics, disease-modifying antirheumatic drugs, and nonsteroidal anti-inflammatory drugs. However, these therapies often lose efficacy over time and compromise immune cell function, increasing the risk of infections and malignancies—a concern that has become more pressing during the ongoing COVID-19 pandemic. The global immunosuppressive state these treatments induce highlights the urgent need for more effective therapeutics to alleviate symptoms without systemic immunosuppression. The Lewis lab aims to design a novel, antigen-specific regulatory vaccine for RA immunotherapy. This involves a dual particle-based system comprising lipid nanoparticles (LNPs) encapsulating mRNA encoding a dendritic cell chemoattractant (GM-CSF) and tolerogenic cytokine (TGF-B1), and poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with an immunomodulatory agent (1α,25-Dihydroxyvitamin D3) and disease-relevant antigen (Type II collagen). We hypothesize that these particles will work synergistically to recruit and modulate dendritic cell phenotype, re-establishing tolerance towards self-antigens. Here, we demonstrated the ability of our immunoparticulates to produce the desired protein and reduce the expression of costimulatory molecules on dendritic cells; which is essential for inducing a tolerant phenotype. The next step would be to elucidate the immunomodulatory effects of the immunoparticulates working cohesively. The insights gained could pave the way for more targeted and translatable immunotherapies, ultimately improving the lives of patients suffering from RA.

In Greek mythology, the Greeks used a ‘Trojan Horse’ to infiltrate the fortress of Troy. Like the Greeks, Cryptococcus neoformans (Cn) is notorious for infiltrating various organs by hitchhiking monocytes across blood vessels. Given Cn’s intrinsic abilities, there is an opportunity to design an effective drug delivery platform. Drugs are often ineffective due to premature clearance from the body and their inability to cross physiological barriers. While nanotechnology has reduced premature clearance, the challenge remains to evade the innate immune system and bypass physiological barriers to accumulate in protected organs. We hypothesize that an avirulent strain of Cn carrying drug-loaded, biomaterial-based nanoparticles will facilitate improved drug delivery. Herein, we investigate two critical aspects of repurposing Cn as a drug carrier: biodistribution and surface engineering. To investigate Cn biodistribution, mice were given bioluminescent Cn via various administration routes. The major organs were harvested and imaged at different time points to measure bioluminescent signals. To engineer the Cn surface, electrostatic adsorption and “click” chemistry were implemented to tether polymeric nanoparticles to Cn. With this work, we have demonstrated that Cn biodistribution is dependent upon the route of delivery and that Cn can traffic to the generally impenetrable brain. Next, we established that polymeric nanoparticles can be stably and efficiently attached to the Cn surface without compromising the its viability, phagocytosability, or vomocytosability. These results suggest that Cn could be a transformative platform to enhance drug delivery! Future work will investigate the effects of attaching particles to the Cn surface on its biodistribution.

Chlamydia is a sexually transmitted disease caused by the bacteria Chlamydia trachomatis in the reproductive tracts of women and men. Women have the highest disease burden, as Chlamydia infections can lead to increased prevalence of cancers, other sexually transmitted infections, and loss of fertility. Even though antibiotics can treat Chlamydia infections, many women are asymptomatic and never receive treatment. Prevention of initial infection via vaccination is a solution, however there are no approved vaccines. We designed a recombinant sub-unit vaccine, self-assembled protein nanocage (SAPN), comprised of coiled coils to display Chlamydia antigens. The coiled coil peptides ZE and ZR form heterodimers due to hydrophobic and electrostatic interactions, and GCN4 peptides trimerize into coiled coils due to hydrophobic interactions. ZE and ZR dimerization drive the assembly of the cage since they are covalently linked to the GCN4 peptides via disulfide bonds. We designed, expressed, and purified fusion proteins of antigens and coiled coils. Antigens displayed include the trimeric major outer membrane protein (MOMP), and the variable domain 4 (VD4) of MOMP displayed on the cage's surface. Portions of polymorphic membrane proteins (pmpEGH) are displayed inside the cage. The assembly and size of cages are confirmed via dynamic light scattering with a diameter of about 200 nm. Immunogenicity of Chlamydia  SAPNs in mice, measured via antigen-specific antibody and T-cell responses, will be presented. Overall, SAPNs provide a modular way to control the oligomeric state of antigens and present them in a more analogous form to their pathogens.