Academic Ascent 2024

“Preparing Your Packet”

Learn about some of the most important elements of preparing your packet for a tenure-track promotion

“Polysorbate Drug Conjugates: Employing Artificial Intelligence and Simulation Approaches to Investigate Pharmacokinetic Properties”

Computational or in silico modeling studies are gold standard techniques to evaluate the drug likeness and pharmacokinetic properties of new chemical entities. However, in silico approaches that rely primarily on Lipinski’s rule of five or molecular weight (less than 500 Daltons) encounter significant obstacles when attempting to predict ADMET properties. Moreover, complex molecules and high molecular weight compounds require specialized models for accurately predicting the results. To address these challenges, artificial intelligence (AI) and machine learning (ML) prediction techniques have recently gained considerable attention, with the goal of predicting ADMET characteristics during the drug discovery process. In our study, we developed a library of polysorbate-drug conjugates for complex diseases such as brain tumor, leishmaniasis and fungal meningitis. To acquire a deeper understanding of the ADMET properties and the ability of these conjugates to cross the blood-brain barrier (BBB), we explored various AI-powered ADMET tools. I will present some of the interesting outcomes on ADMET properties derived from AI/ML applications and BBB simulation results. Our research will offer perspectives on leveraging AI platforms to comprehend the ADMET properties of high molecular weight compounds.

“Mastering Pre-Interview”

Learn about how to best represent yourself to faculty hiring committees in the initial first interviews and what’s important to help you move to the more advanced stages of the hiring process.

“Towards Ingestible Robots to Support Living Therapeutics”

Living therapeutics such as engineered probiotics have great potential to treat disease. They are typically administered by the oral route, which presents a formidable environment against the viability of these living drugs. In this talk, I will share our work in developing ingestible depots that support the viability of these living therapeutics in the gastrointestinal tract using soft materials and device approaches.

“Mastering Onsite Interview”

Learn about how to prepare and present your career and vision in the important onsite interview, including the highly-regarded Chalk Talk presentations, when interviewing with faculty, administration, and hiring committee personnel.

“AGILE Platform: A Deep Learning-Powered Approach to Accelerate LNP Development for mRNA Delivery”

Dr. Xu has built the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry. AGILE streamlines the iterative development of ionizable lipids, crucial components for LNP-mediated mRNA delivery. This approach brings forth three significant features: efficient design and synthesis of combinatorial lipid libraries, comprehensive in silico lipid screening employing deep neural networks, and adaptability to diverse cell lines. The AGILE platform can be able to rapidly design, synthesize, and evaluate new ionizable lipids for mRNA delivery in muscle and immune cells, selecting from a library of over 10,000 candidates.

“Starting Up Lab”

Learn the key pillars of starting your lab and getting it off the ground, with an overview on best practices on managing the research, personnel, and funding aspects of a burgeoning lab.

“Building Next-Generation Human In Vitro Multicellular Models” 

In the last decade, human organoid models have become increasingly accessible, opening new avenues for high-throughput studies ranging from disease modeling to drug discovery. In parallel, progress in bioprinting technologies is paving the way towards fabricating transplantable lab-grown organs. Between these two drastically different scales and throughputs, however, there remains a gap to be filled: we are still in need of mesoscale in vitro models harboring sufficient complexity to accurately mimic interactions between multiple cell or tissue types, while simultaneously remaining simple enough to allow for mechanistic studies, which require meticulous isolation and manipulation of biological variables. My research leverages novel biofabrication approaches to increase the complexity of human in vitro multicellular models, ranging from respiratory organs to neuromuscular tissues. First, I will present a 3D model of the human airway epithelium amenable to high-resolution live microscopy at the air-liquid interface, overcoming structural challenges of existing model systems and enabling investigation of the interactions between respiratory pathogens and airway mucus, Second, I will present ongoing research in controlling environmental cues to improve the maturity of human neuromuscular junction models, which could ultimately be used to explore new therapeutic options for neurodegenerative diseases such as amyotrophic lateral sclerosis. Overall, by bridging the gap between microscale models for high-throughput screening and macroscale models for regenerative medicine, mesoscale tissue models have the potential to become a versatile tool for fundamental and translational questions alike.