The research activities in my laboratory have been centered around the field of molecular neuroscience, with two main interests, namely, the study of the pathophysiology of neuropsychiatric childhood disorders and the molecular neurobiology of the sense of olfaction. Regarding the first topic, my group is interested in studying neurodevelopmental pediatric diseases that have well-known genetic etiologies, which represents a window of opportunity not only to understand the participation of genes involved in developmental processes, but also to discover pathophysiological mechanisms that can lead to the generation of new therapeutic strategies. Two genetic diseases have been mostly studied by our team: Pitt-Hopkins Syndrome, a childhood genetic disease characterized by severe motor and cognitive delay, caused by haploinsufficiency of the TCF4 gene, which encodes a poorly characterized bHLH transcription factor; and the syndrome related to the CNTNAP2 gene, which has altered phenotypes similar to Pitt-Hopkins Syndrome. The mechanisms by which TCF4 haploinsufficiency results in Pitt-Hopkins Syndrome are not fully understood, nor it is known if the molecular mechanisms behind the disorders caused by mutations in TCF4 and CNTNAP2 have an overlap. We seek to unravel the genetic, molecular, and cellular bases of these disorders, using patient-derived and mutant human cell lines and cerebral organoids as model systems in vitro, as exemplified by the publications below. Our long-term goal is to identify altered pathways that can become pharmacological targets, as well as obtain proof-of-concept that gene therapy strategies can be applied to those disorders.
Another line of investigation in my lab seeks to decipher the function of olfaction in controlling motivated behaviors, such as reproduction, aggression, territoriality, and parental behavior. My team has used the mouse as a model to explore stereotyped behaviors induced by olfactory stimuli and to understand how these cues are detected by the olfactory sensory organs from a molecular and cellular standpoint. We have also studied the role of hormones, particularly oxytocin, in mediating these behavioral changes and how olfactory information is internally represented and processed in the brain. Numerous collaborations have been established by my group throughout the years, the most fruitful of which have been with Profs. Lisa Stowers (Scripps Research), Darren Logan (Welcome Trust Sanger Institute, UK), and Alysson Muotri (UCSD).