Welcome to the Machaca Lab!
We are interested in understanding intracellular signaling pathways under physiological conditions and how they are disrupted under pathological conditions.
Current research efforts in the Lab are focused on three broad areas using a combination of animals models (currently mouse and Xenopus), microscopy, cell physiology, genetic, and biochemical approaches:
1. Ca2+ signaling & ER-plasma membrane contact sites (ERPMCS).
We are interested in the regulation of Ca2+ signaling during cellular differentiation and under disease states with a focus on store-operated Ca2+ entry (SOCE). We are investigating the role of SOCE in various organ functions including in adipose. In addition, we are exploring the physiological role of Ca2+ tunneling, a signaling modality that requires both SOCE and IP3-dependent Ca2+ release from stores to induce cortical Ca2+ signals. Ca2+ tunneling is emerging as important signaling pathway in secretory tissues.
Ca2+ signaling papers
2. Nongenomic progesterone signaling.
In addition to its classical signaling through nuclear receptors, progesterone signals on a faster timescale through multi-pass membrane receptors that do not involved transcription (hence the term nongenomic). We are using Xenopus oocyte maturation as a model system to elucidate the poorly understood early steps in nongenomic progesterone signaling and translating those findings to mouse models.
P4 nongenomic signaling papers
3. Cellular models to empower personalized medicine.
Personalized medicine is centered on the ability to deeply phenotype the disease in question in a personalized fashion to better inform clinical care. In collaboration with clinicians at SIDRA, we are combining multiomic phenotyping of pediatric patients suffering from immunodeficiencies with patient-specific cellular models to better define the pathology in rare cases with unknown prognosis. We employ different approaches including CRISPR, overexpression/knock down, primary patient cells, etc. to define the pathology.
Personalized medicine papers