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

Women of African descent are disproportionately affected by the HIV epidemic. One of the major drivers of the HIV epidemic is bacterial vaginosis (BV), a prevalent vaginal syndrome that is often associated with a multitude of other sexual and obstetric complications. AI and machine learning present opportunities for analyzing data for diagnosing BV, which has been demonstrated in prior works focusing on female cohorts in the United States. In this work, we implement four machine learning models for predicting BV in a cohort of women from Tanzania, Africa living with HIVusing 16S rRNA sequencing data. We find that model performance for indicating BV in this African cohort was lower compared to prior works using cohorts from the United States. Results indicated that intermediate Nugent scores posed challenges for model discrimination, often leading to misclassification. Interestingly, we find Lactobacillus iners, typically found to be less resistant to BV, to be a significant predictor of BV among this cohort. These findings point to new areas of investigation for improving the feasibility and equity of predictive diagnosis of BV involving women with vaginal and sexual disorders and conditions.

This study explores the optimization of enzymes produced by Aspergillus niger, isolated from central Uganda, to enhance the cookability of key African staple foods, including dry beans, cooked bananas, corn (maize) meal, and millet meal. The enzymes cellulase, hemicellulase, pullulanase, and protease were cultivated and characterized for their efficacy. Enzyme-treated samples demonstrated significant advantages, including reduced cooking times, water and energy savings, improved texture, and minimized food waste. This research not only highlights the potential of local fungal strains for sustainable food processing but also aims to contribute to food security and resource efficiency in Africa.

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.

Of children born with sickle cell disease, 11% will have a major stroke by age 16, and 30-35% will have a silent stroke impairing cognitive abilities. Later in life, risk for hemorrhagic stroke increases, suggesting an age-related component to arterial damage. Significantly higher velocities measured with transcranial Doppler in cerebral arteries implicates children at risk for strokes with disturbed cerebral hemodynamics. Cathepsins are a family of proteases containing the most potent human elastases and collagenases that we have shown to be upregulated by disturbed blood flow and by inflammatory stimuli, known to be elevated in sickle cell disease. It is unclear, however, how biomechanical and biochemical stimuli integrate to accelerate pathological remodeling of large arteries in these children. We will present our multiscale approach and results demonstrating these links between disturbed blood flow and chronic inflammation due to sickle cell disease, from the cellular level to transgenic animal models up through human computational fluid dynamics to identify new targets to prevent this accelerated artery damage affecting those born with this genetic disease and aging related implications.

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.

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.

The global production of dairy products increases daily but generates byproducts such as whey, which can negatively affect the environment when dumped into waterways. This is a questionable practice due to the components that can be used and economically benefit processors. The objective of this research was to develop a symbiotic fermented milk drink. The fermentation was carried out conventionally, comparing the culture of Lactobacillus rhamnosus with commercial mixed culture. Parallel to the fermentation, an enzymatic reaction was carried out to produce galactooligosaccharides; the product of this was mixed separately with the two fermented drinks obtained from the two cultures used, in proportions 1:3 and 1:4. The enzyme β-galactosidase from Aspergillus oryzae was used at 50 °C for the enzymatic reaction. The quantification of galactooligosaccharides was determined with a Benson column (Na+ sulfonated polystyrene divinylbenzene) at 80 °C, operated with an HPLC system (Thermo) equipped with a Shodex RID101A refractive index detector. The fermentation process was carried out at a temperature of 43 °C until lactic acid percentages between 0.75% and 1.5% were reached. The commercial culture fermented in shorter times, with greater yield and doubling speed. The achieved value of total galactooligosaccharides in fermented milk was 1.087% m/m, thanks to the high initial concentration of lactose in the enzymatic reaction medium. The final probiotic content was 2x10^7 for Lactobacillus rhamnosus and 8x10^7 CFU/ml for the commercial one. The drink did not present significant changes during 30 days of storage.

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.