Research in the Alex Kolodkin Laboratory is focused on understanding how neuronal connectivity is established during development. Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology and synapse formation and function. We have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors. We employ a cross-phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology and synaptogenesis. We also seek to understand how these signals are transduced to cytosolic effectors. Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function. Our current work includes a relatively new interest in understanding the origins of laminar organization in the central nervous system.

The Jeremy Nathans Laboratory is focused on neural and vascular development, and the role of Frizzled receptors in mammalian development. We use gene manipulation in the mouse, cell culture models, and biochemical reconstitution to investigate the relevant molecular events underlying these processes, and to genetically mark and manipulate cells and tissues. Current experiments are aimed at defining additional Frizzled-regulated processes and elucidating the molecular mechanisms and cell biologic results of Frizzled signaling within these various contexts. Complementing these areas of biologic interest, we have ongoing technology development projects related to genetically manipulating and visualizing defined cell populations in the mouse, and quantitative analysis of mouse visual system function.

Our mission is to reveal the molecular logic of our intelligence in health and disease. We use advanced molecular biological tools and state-of-the-art neuroscience to test the role of synaptic and neuronal molecules in the dynamics of the living brain.

Artificial neural networks have been heavily inspired by the brain’s architecture, guiding our journey to discovering the keys to intelligence. We now find ourselves at a pivotal moment: today's AI systems surpass biological circuits in certain tasks, yet we still lack a fundamental understanding of the mechanisms behind the brain’s superior cognitive flexibility and efficiency. At Ingie Hong’s Quantitative Intelligence Lab, we are dedicated to unraveling the principles that enable the mammalian cortex to achieve remarkable feats of intelligence, including rapid learning, generalization, and inference across vast stores of memory.

A single neuron’s response depends on its synaptic connections and intrinsic properties, which are dictated by the expression of neuronal genes. However, the role of these molecules in brain computations remains largely uncharted territory. Focusing on the mouse visual cortex as a starting point for broader generalization, and using large-scale electrophysiology, advanced microscopy, and machine learning, we have begun to uncover the impact of key synaptic genes on cortical processing and their role in the brain’s “working algorithm” (Hong et al., Nature, 2024). Our molecular tools, including gene therapy vectors and antisense oligonucleotides, show promise as effective therapeutic candidates.

Our research will advance the nascent field of 'neurocomputational therapeutics'—innovative genetic and pharmacological tools that address biases in neural activity. These tools will not only facilitate the development of novel mechanism-based treatments for brain disorders but also inspire the next generation of intelligent artificial neural networks.

Research efforts in the Edward Chen Lab focus on bleomycin-induced pulmonary fibrosis and granulomatous inflammation as well as clinical and translational studies in sarcoidosis. Our studies have included topics such as the etiologies of sarcoidosis, hylleraas hydride binding energy in diatomic electron affinities, and molecular convergence of neurodevelopmental disorders. We have also investigated the use of quantitative mass spectrometric analysis to better understand the mechanisms of phospho-priming and auto-activation of the checkpoint kinase Rad53 in vivo.