Biography

Trained at the National University in Mexico City, Mexico and the University Louis Pasteur in Strasbourg, France, Dr. Araceli Espinosa-Jeffrey is a full-time neurobiologist and holds a Full Research Scientist position at the Intellectual and developmental disabilities Research Center formerly known as the Mental Retardation Research Center at UCLA.

Dr. Espinosa’s early work included studies of brain cells in culture at the CINVESTAV in Mexico City. She moved to France where she obtained her Ph.D. working on the isolation and characterization of culture conditions for oligodendrocytes, the myelin forming cells in the Central Nervous System. Much of her work involved the design of chemically defined media for progenitors and mature oligodendrocytes. Dr. Espinosa’s research focuses on understanding the repair of Central Nervous System (CNS) damage caused by disease or injury. Her principal research deals with increasing the number of oligodendrocytes to synthesize and maintain myelin in the myelin deficient central nervous system. These studies use two animal models of myelin deficiency to investigate mechanisms of remyelination and to study techniques for promoting remyelination. The first animal model, the myelin deficient mutant rat (md rat) presents severe dysmyelination and her transplantation studies have shown that healthy grafts display cell migration, maturation and functional integration in the md host brain.

During the past decade, she demonstrated that oligodendrocytes synthesize and secrete the iron carrier protein transferrin and that transferrin is an essential protein for myelination because it upregulates the myelin basic protein gene. Knowing that oligodendrocytes have a dual function in the CNS: myelination and preservation of iron homeostasis, is a key point when addressing injury and repair of the CNS. Therefore, part of her research efforts focus on assessing how iron metabolism is involved in dys- and de-myelinating diseases. In collaboration with the Pasteur Institute she studied how the over-expression of the human transferrin gene in the brain affects myelination.

The second animal model (4e) is a transgenic mouse overexpressing the proteolipid gene (PLP/myelin gene). These animals myelinate normally but their CNS demyelinates gradually leading to hind limb impairment mimicking to some extent demyelination occurring in patients with multiple sclerosis. In collaboration with Dr. K Ikenaka in Okazaki, Japan, Dr. Espinosa has examined the improvements obtained when non transgenic oligodendrocytes are grafted into the brain of these hosts. She showed that grafted cells survive, migrate to areas where naked axons are found and myelinate them. The neurological improvements include phenotype reversal in a sustained manner by the recovery of hind-limb function.

Dr. Espinosa has been using neural stem cells in culture aiming at understanding the factors influencing their behavior and specific needs to move from a quiescent multipotent stage to an active stage in culture. Her cell culture studies have been instrumental for the characterization of the commitment of NSC to oligodendrocytes. Much of her work has been directed towards evaluating the efficacy of specific combinations of neurotrophic factors to mobilize “endogenous” neural stem cells in animal models of white matter disorders. At the present time Dr. Espinosa is testing the efficacy of treatments designed to stimulate endogenous neural stem cells to become oligodendrocytes and remyelinate axons in two models of perinatal white matter injury (WMI): The md rat and a model of glutamate excitotoxicity. She is also evaluating the neuroprotective properties of a specific combination of these factors in neonatal mice exposed to excitotoxic insults.

Dr. Espinosa in collaboration with Dr. Stephane Woerly, has been exploring the endogenous capabilities of repair in the adult injured spinal cord and she has demonstrated that the repair process not only consists of regeneration of pre-existing neurons but also the formation of new neurons after having repaired the lesion with a hydrogel. Neural stem cells from the central canal give rise to migratory nestin expressing progenitors that populate the gel implant and this phenomenon continues several months after reconstruction of the injured spinal cord. This work provides new insights on the concept of regeneration and repair of the central nervous system.

One aspect of her research in collaboration with UCLA colleagues is devoted to obtaining oligodendrocytes from human induced pluripotent stem cells (iPS) cells in defined conditions in the absence of animal products. This work has a potential direct application to the clinical use of oligodendrocytes derived from stem cells for the treatment of children with genetic or acquired myelin disorders. Through the years Dr. Espinosa has established several intramural collaborations with Drs. John Edmond and Ivan Lopez studying the effects of pre- and postnatal carbon monoxide exposure on brain development; with Drs. Mike Levine and Carlos Cepeda on calcium modulation of dopamine potentiation of N-methyl-D-aspartate responses. She also collaborates with Dr. Milan Fiala on the enhancement of amyloid-β uptake by macrophages of Alzheimer’s disease patients and exploring ways to correct immune defects of Alzheimer’s disease patients with a previously uncharacterized approach to AD immunotherapy.

Her most recent accomplishments are the establishment of novel approaches to increase neural cell proliferation using simulated microgravity. She discovered simulated microgravity to be an excellent strategy to increase neural cell numbers without performing genetic manipulation or long-term treatments with mitogens. This original and completely different approach provides a platform opening new fields of research using gravitational science for regenerative medicine, particularly to address neurodegenerative and developmental disabilities. These studies are of particular interest for astronaut health as the metabolic changes reported occurred in just 3 days. Most astronauts stay in the International Space Station six months and it has been reported that microgravity induces intracranial hypertension in astronauts while in space. This condition persists when they come back to earth, representing a risk factor for long-duration space missions.

A NASA-sponsored International Space Station investigation entitled: “The Impact of Real Microgravity on the Proliferation of Human Neural Stem Cells and derived-Oligodendrocytes”, has been scheduled to fly in Space X-16 on November 29, 2018. Dr. Espinosa believes that there may be molecules that may be secreted by cells in microgravity impossible to unveil while in the 1G environment (i.e. earth gravity). This mission is of critical importance as it relates to NASA Space Biology and NASA Human Research Programs’ efforts to pioneer research in this area for fundamental science, support human space exploration, and return data for Earth-benefits.

She discovered simulated microgravity to be an excellent strategy to increase neural stem cells (NSCs) numbers without genetic manipulation or long-term mitogen treatment. Thus, she provided a novel platform for research using gravitational science for neuro-regenerative medicine.

Astronauts present a new syndrome “Vision Impairment and Intracranial Pressure” (VIIP) and Espinosa hypothesized that new brain cells contribute to VIPP. Her studies are critical for space exploration and astronaut wellbeing as she discovered that Human NSCs proliferate more while in space. Moreover, these cells seem to remember having been in space and continue proliferating more after space flight. In addition, upon returning from space most NSCs are larger than the ground control cells. The above-mentioned properties may contribute to the increased intracranial hypertension observed in astronauts.

Dr. Espinosa is now analyzing the secretome of cells grown in space to identify molecules and pathways that would be used to harness approaches to modulate NSCs proliferation in space and after space flight.