Dr. Aparna Bhaduri earned a B.S in Biochemistry and Cell Biology and a B.A in Political Science from Rice University in 2010. She completed her doctoral studies at Stanford University in Cancer Biology in 2016, where she focused on epithelial tissue differentiation and neoplasms She was a postdoctoral scholar at the University of California San Francisco in the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, in the lab of Dr. Arnold Kriegstein. As a postdoctoral scholar, she has used single-cell RNA sequencing to characterize cell types in the developing cortex across cortical areas, in human and non-human primates, and in glioblastoma. Because experimental manipulations of the developing human cortex will require in vitro models, she has been using similar approaches to compare cells types in organoid models and primary tissues. Her long-term interests to be pursued in her own independent laboratory at UCLA are in understanding how stem cells during cortical development give rise to the human brain, and how aspects of these developmental programs can be hijacked in cancers such as glioblastoma. One aspect of normal development and cancer that particularly interests her is the role of metabolism in regulating cell fate and tissue homeostasis. In order to explore these questions, Aparna uses single-cell genomics, informatic analysis, and organoid models. In her free time, she enjoys spending time with her husband rock climbing, biking, and cooking.
The Bhaduri lab studies how the human brain develops, and how the cells and trajectories of normal brain development are re-activated in brain tumors such as glioblastoma. They use the concept of cell type to group cells based upon common features. This strategy enables them to find the genes or other properties of cells that define one population and distinguish it from others, enabling many comparisons between primary human brain samples, cortical organoids, and glioblastoma tumors. Only recently has technology given us an opportunity to interrogate cells within the brain one at time, and to look at their transcriptome with a strategy called single-cell RNA sequencing. Dr. Bhaduri has led efforts as part of the BRAIN Initiative consortium to profile and identify the cell types that exist across the developing human brain from early stages of human brain development to the mid-stages where the peak of neuron birth occurs. This approach has highlighted similarities and differences across brain regions and across the different parts of the cerebral cortex, the top layer of the human brain that enables a variety of cognitive and perception functions. Now with a broad stroke understanding of the cell types that exist and how they change, Dr. Bhaduri is seeking to use cortical organoids to better understand the intrinsic and extrinsic cells that really instruct the various stem cell populations in the developing human brain to make the myriad cell types they give rise to.
Laura DeNardo, Ph.D. is an Assistant Professor in the Department of Physiology in the David Geffen School of Medicine at UCLA. She received a dual BA in Molecular and Cell Biology and Art Practice from UC Berkeley in 2007. She went on to receive a Ph.D. in Neurosciences from UC San Diego, where she worked with Dr. Anirvan Ghosh. As a graduate student, she elucidated mechanisms governing the development and function of hippocampal synapses. Her work identified a key molecular mechanism by which individual neurons can independently regulate the development of specific classes of synapses in distinct dendritic compartments. Beginning in 2013, she carried out her postdoctoral fellowship with Dr. Liqun Luo at Stanford University. As a postdoc, Dr. DeNardo used new viral-genetic tools to map cortical microcircuits. Focusing on the medial prefrontal cortex (mPFC), she identified important departures from the canonical microcircuit organization that has been well-characterized in sensory cortices. To understand how neuronal circuits control behavior, she developed a new knock-in mouse for activity-dependent genetic labeling (TRAP2) that is being widely adopted by the global Neuroscience community. Using TRAP2, she has elucidated the organization and function of mPFC circuits that contribute to long-term memory. Dr. DeNardo will open her lab at UCLA in January, 2019.
Research in the DeNardo lab aims to understand how mPFC is organized to promote specific behaviors. Do particular classes of mPFC projection neurons mediate different behaviors, or do the same classes of mPFC neurons adapt their function to promote different behavioral outcomes? How are these circuits assembled during development? Using innovative viral-genetic tools, novel transgenic mice, and whole-brain imaging technologies, we aim to define the connectivity and function of mPFC cells underlying adaptive behaviors and to identify molecular cues that wire these circuits during development.
Identifying the molecular underpinnings of neural-circuitry assembly has long been a goal of neuroscience research. Much progress has been made by studying conserved circuitry in model organisms, which can be applied to the human nervous system. There are, however, remaining challenges for investigating the genetic pathways that lead to the formation of primate- or human- specific neural structures. Without these, elucidating the roots of cognitive behaviors is impossible, as is pinpointing the pathogenetic causes of neurological disorders and neural degenerative diseases. The central goal of the research in Dr. Peng’s lab is understanding the cellular and molecular basis of the functional evolution of neural structures in primates. Her lab focuses on the visual system as the entry point into these questions.
The visual system accounts for a substantially expanded area of the human brain and supports multiple cognitive functions in humans. The genetic basis that accounts for these evolutionary changes remains unclear. Compared to other mammals, humans and other primates do not see well in dim light nor detect fast motion, but can perceive the finest details at the center of their gaze. Humans rely on this clear vision, so called “high-acuity vision,” for reading, driving, facial recognition, and other cognitive functions. High-acuity vision stems from a specialized neural structure, called “fovea,” located at the center of the retina. Humans and other primates are the only mammalian species with foveae in their retinas (Figure). The research supported by the Klingenstein-Simons fellowship aims to address two basic, albeit important, questions: 1) How is the fovea formed? And 2) Why did the fovea form in primates? To this end, the project establishes an innovative cross-species research paradigm and utilizes a suite of advanced next-generation sequencing methods to seek the molecular and genetic basis of foveal evolution and development. The research will combine genetic manipulation and functional assays to identify the genetic mechanism that mediates foveal formation.
