Christopher H. Chen, Ph.D. - US grants
Affiliations: | 2009-2016 | Neuroscience | Albert Einstein College of Medicine, New York, New York, United States |
2016- | Neuroscience | Harvard Medical School, Boston, MA, United States |
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Christopher H. Chen is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
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2016 — 2021 | Chen, Christopher S (co-PI) [⬀] Seidman, Christine E Seidman, Jonathan G |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Defining Genetic Architecture and Pathways of Dcm @ Harvard Medical School ABSTRACT Heart failure (HF), a leading cause for cardiac transplantation and premature death, is usually preceded by ventricular dilatation and diminished systolic performance or dilated cardiomyopathy (DCM). DCM has many etiologies, including damaging variants in genes with diverse functions in cardiac biology. During the prior funding period we showed that the most common genetic cause of DCM was truncating variants in titin (TTNtv). These account for 25% of familial and 12% of sporadic DCM and for ~10% of DCM that occurs with pregnancy, alcohol abuse, and after cancer therapies. In addition, ~0.2% of the general population carries a TTNtv; these individuals have substantially higher lifelong risks for developing DCM and heart failure. We also identified mechanisms by which TTNtv and other recently recognized DCM genes (FLNC and ALPK3) cause disease. With this competitive renewal we propose to focus on the discovery of genes and mechanisms that account for unexplained DCM, which remains an unmet need. We propose that some unexplained DCM is mechanistically related to established genetic causes and results from sequence variants that are not routinely interrogated, or that have unclear functional consequences. We will study the roles of somatic variants, non-coding regulatory variants, mitochondrial variants, and variants of unknown significance (VUS) in established and newly identified DCM genes. We will also define cell populations and transcriptional profiles of all cells in human hearts with unexplained DCM and DCM with established genetic etiologies, so as to identify shared or distinct pathways that may inform therapeutic opportunities. Our analyses will employ state-of-the art technologies. We will exploit whole genome sequencing (WGS) from blood- and cardiac tissue-derived DNAs obtained from unexplained DCM subjects. We will use single nuclear RNA sequencing (NucSeq) to define how cell populations and transcription change in DCM hearts in comparison to normal hearts, using our recently completed normal human heart NucSeq data. We will perturb new identified variants and mechanisms in iPSC-CMs and mouse models. These studies will improve knowledge of the molecules and pathways that enable normal heart function, the molecular causes and mechanisms of DCM, information that will improve diagnosis and inform precision therapies to prevent heart failure. Our analyses will also contribute functional insights into noncoding sequences. To accomplish these goals, we will: 1) Identify coding and non-coding, germline and somatic variants that contribute to unexplained DCM; 2) Define perturbed cell populations and associated transcriptional profiles in hearts from variant-positive and unexplained DCM; 3) Define DCM mechanisms using engineered iPSC-CMs and mouse models. |
0.915 |
2017 — 2019 | Chen, Christopher [⬀] | F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
@ Harvard Medical School Project Summary The cerebellum has well-appreciated roles in motor behaviors, and increasingly well-established roles in nonmotor behaviors. Cerebellar dysfunction is known to cause ataxia, dystonia, and even some of the social deficits found in autism This wide array of functions is thought to be supported by the cerebellum's connections with structures throughout the brain. However, aside from a few canonical output pathways related to motor pathways, little is known about how else the cerebellum can modulate the rest of the brain. To improve our understanding of cerebellar output pathways, this proposal seeks to generate a connectivity map based on visualizing synapses from cerebellar output neurons. Next, as a first step in describing the synaptic properties underlying all cerebellar outputs, I will closely examine the properties underlying transmission of information at a relatively known output: the cerebellothalamic synapse. While this connection has been anatomically described, remarkably little is known about its synaptic properties. The computations within the cerebellum are overwhelmingly linear. It might follow that this linearity is a property that persists all the way to cerebellar outputs. Because cerebellar outputs are spontaneously active at relatively high rates, all cerebellar output targets will likely have specific mechanisms to encode this continuous barrage of activity. Thalamic neurons might be specialized for this purpose because they have two modes of operation: a nonlinear mode that can ?gate? inputs, and a linear one that faithfully relays inputs. Preliminary data indicates that these modes are dependent on whether the animal is stationary or moving. I hypothesize that the nonlinear mode of the thalamus can function as a gate to filter out spontaneous, ?noisy? cerebellar activity, and reliable and precise activity is only relayed from the thalamus in the linear mode. I will test these ideas by combining optogenetics, dynamic clamp, and whole cell recordings in vitro and in vivo with behavioral measurements during a lever pressing task. Completion of this project will unveil novel cerebellar output pathways, and demonstrate methods by which the brain can gate and transmit information. |
0.915 |
2020 | Chen, Christopher [⬀] | K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. |
Cerebellar Outputs Through An Unconventional Nucleus @ Harvard Medical School The cerebellum is no longer just a motor structure. Human imaging studies have pointed to links between the cerebellum and cognition, language, and affect. Preclinical work has also indicated that the cerebellum has many nonmotor functions ranging from aggression to sleep. Expression of autism related proteins within cerebellar principle neurons (Purkinje cells) is sufficient to recapitulate many hallmarks of the condition in mice. These Purkinje cells send their projections to the deep cerebellar nuclei (DCN) and vestibular nuclei (VN), often considered the only cerebellar output nuclei. However, the known output pathways that connect the cerebellum with the forebrain seem insufficient to explain the diversity of behaviors now associated with it. We found that there is an additional, underappreciated output pathway through the parabrachial nucleus that receives direct Purkinje cell input and projects to the forebrain. Unlike the conventional cerebellar outputs, this pathway has significant projections to the amygdala, basal forebrain, prefrontal cortex and others. The aim of this project is to characterize cerebellar inputs to the parabrachial and identify these novel cerebellar output targets. We will focus on the projection to the amygdala. There is a rich behavioral literature describing the cerebellum as a core component in fear extinction, though there is no known neural substrate underlying this. In humans, trauma to the cerebellum is a strong predictor of post- traumatic stress disorder. We will test whether this unconventional cerebellar output can potentially mediate this nonmotor behavior. |
0.915 |