Dr. Rafael Demarco | Demarco Lab

Bio:

I am a new Assistant Professor in the Department of Biology at the University of Louisville whose ultimate goal is to understand how changes in metabolism impact stem cell behavior during homeostasis, aging and stress conditions. I was trained as a geneticist during my Ph.D. with Dr. Erik Lundquist at the University of Kansas, where I learned to ask questions and interpret genetic data using model organisms. To pursue my objective of studying stem cells and their niches, I obtained my postdoctoral training and later position as a Research Specialist in the laboratory of Dr. Leanne Jones (first at the Salk Institute and then at the University of California, Los Angeles and San Francisco), a leading expert in the fields of stem cells and current director of the Bakar Aging Research Institute at UCSF. During my time working with Dr. Jones, I developed my own research interests focusing on how different aspects of metabolism impact the stem cell niche present in the Drosophila testis. Unexpectedly, I found that both stem cell populations present in the testis niche employ mechanisms to maintain proper lipid homeostasis in order to prevent stem cell loss. Disruptions in either mitochondrial fusion (in germline stem cells1) or autophagy (in cyst stem cells2) led to deficient lipid catabolism and ectopic accumulation of lipids in the stem cell niche, which promoted stem cell loss through differentiation. Hence, a model has emerged revealing a novel metabolic facet in the regulation of stem cell fate, which appears conserved across stem cell systems3. In my recently established laboratory, I am engaged in pursuing the mechanism(s) through which ectopic lipid accumulation can impact stem cell fate within the niche, which could shed light into the development of new strategies targeting stem cell-based regenerative therapies.

Abstract:

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for male germline stem cell (GSC) maintenance in Drosophila melanogaster.  Depletion of Mitofusin (dMfn) or Optic atrophy 1 (Opa1) led to dysfunctional mitochondria, activation of Target of Rapamycin (TOR), and a dramatic accumulation of lipid droplets (LDs). Pharmacologic or genetic enhancement of lipid utilization by the mitochondria decreased LD accumulation, attenuated TOR activation and rescued GSC loss caused by inhibition of mitochondrial fusion. However, the mechanism(s) leading to GSC loss were unclear. TOR activation has been demonstrated to suppress JAK-STAT signaling by stabilizing the JAK-STAT inhibitor SOCS36E. As JAK-STAT signaling is critical for regulating stem cell self-renewal in the testis, we wanted to test the hypothesis that the increase in TOR activity in early germ cells would lead to SOCS36E stabilization, which in turn, could contribute to stem cell loss.  Indeed, we found that SOCS36E levels were higher in early germ cells upon depletion of dMfn or Opa1. Subsequently, we show that activation of the JAK-STAT pathway, but not BMP signaling, is sufficient to rescue loss of GSCs as a result of the block in mitochondrial fusion.  In addition, preliminary genetic and proximity-labeling data suggest that LD accumulation acts in parallel to TOR/SOCS36E to promote GSC loss. Our findings highlight a critical role for mitochondrial metabolism and lipid homeostasis in GSC maintenance, providing a framework for investigating the impact of metabolic diseases on stem cell function and tissue homeostasis.

Dr. Rafael Demarco | Demarco Lab

Bio:

I am a new Assistant Professor in the Department of Biology at the University of Louisville whose ultimate goal is to understand how changes in metabolism impact stem cell behavior during homeostasis, aging and stress conditions. I was trained as a geneticist during my Ph.D. with Dr. Erik Lundquist at the University of Kansas, where I learned to ask questions and interpret genetic data using model organisms. To pursue my objective of studying stem cells and their niches, I obtained my postdoctoral training and later position as a Research Specialist in the laboratory of Dr. Leanne Jones (first at the Salk Institute and then at the University of California, Los Angeles and San Francisco), a leading expert in the fields of stem cells and current director of the Bakar Aging Research Institute at UCSF. During my time working with Dr. Jones, I developed my own research interests focusing on how different aspects of metabolism impact the stem cell niche present in the Drosophila testis. Unexpectedly, I found that both stem cell populations present in the testis niche employ mechanisms to maintain proper lipid homeostasis in order to prevent stem cell loss. Disruptions in either mitochondrial fusion (in germline stem cells1) or autophagy (in cyst stem cells2) led to deficient lipid catabolism and ectopic accumulation of lipids in the stem cell niche, which promoted stem cell loss through differentiation. Hence, a model has emerged revealing a novel metabolic facet in the regulation of stem cell fate, which appears conserved across stem cell systems3. In my recently established laboratory, I am engaged in pursuing the mechanism(s) through which ectopic lipid accumulation can impact stem cell fate within the niche, which could shed light into the development of new strategies targeting stem cell-based regenerative therapies.

Abstract:

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for male germline stem cell (GSC) maintenance in Drosophila melanogaster.  Depletion of Mitofusin (dMfn) or Optic atrophy 1 (Opa1) led to dysfunctional mitochondria, activation of Target of Rapamycin (TOR), and a dramatic accumulation of lipid droplets (LDs). Pharmacologic or genetic enhancement of lipid utilization by the mitochondria decreased LD accumulation, attenuated TOR activation and rescued GSC loss caused by inhibition of mitochondrial fusion. However, the mechanism(s) leading to GSC loss were unclear. TOR activation has been demonstrated to suppress JAK-STAT signaling by stabilizing the JAK-STAT inhibitor SOCS36E. As JAK-STAT signaling is critical for regulating stem cell self-renewal in the testis, we wanted to test the hypothesis that the increase in TOR activity in early germ cells would lead to SOCS36E stabilization, which in turn, could contribute to stem cell loss.  Indeed, we found that SOCS36E levels were higher in early germ cells upon depletion of dMfn or Opa1. Subsequently, we show that activation of the JAK-STAT pathway, but not BMP signaling, is sufficient to rescue loss of GSCs as a result of the block in mitochondrial fusion.  In addition, preliminary genetic and proximity-labeling data suggest that LD accumulation acts in parallel to TOR/SOCS36E to promote GSC loss. Our findings highlight a critical role for mitochondrial metabolism and lipid homeostasis in GSC maintenance, providing a framework for investigating the impact of metabolic diseases on stem cell function and tissue homeostasis.

Dr. Rafael Demarco | Demarco Lab

Bio:

I am a new Assistant Professor in the Department of Biology at the University of Louisville whose ultimate goal is to understand how changes in metabolism impact stem cell behavior during homeostasis, aging and stress conditions. I was trained as a geneticist during my Ph.D. with Dr. Erik Lundquist at the University of Kansas, where I learned to ask questions and interpret genetic data using model organisms. To pursue my objective of studying stem cells and their niches, I obtained my postdoctoral training and later position as a Research Specialist in the laboratory of Dr. Leanne Jones (first at the Salk Institute and then at the University of California, Los Angeles and San Francisco), a leading expert in the fields of stem cells and current director of the Bakar Aging Research Institute at UCSF. During my time working with Dr. Jones, I developed my own research interests focusing on how different aspects of metabolism impact the stem cell niche present in the Drosophila testis. Unexpectedly, I found that both stem cell populations present in the testis niche employ mechanisms to maintain proper lipid homeostasis in order to prevent stem cell loss. Disruptions in either mitochondrial fusion (in germline stem cells1) or autophagy (in cyst stem cells2) led to deficient lipid catabolism and ectopic accumulation of lipids in the stem cell niche, which promoted stem cell loss through differentiation. Hence, a model has emerged revealing a novel metabolic facet in the regulation of stem cell fate, which appears conserved across stem cell systems3. In my recently established laboratory, I am engaged in pursuing the mechanism(s) through which ectopic lipid accumulation can impact stem cell fate within the niche, which could shed light into the development of new strategies targeting stem cell-based regenerative therapies.

Abstract:

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for male germline stem cell (GSC) maintenance in Drosophila melanogaster.  Depletion of Mitofusin (dMfn) or Optic atrophy 1 (Opa1) led to dysfunctional mitochondria, activation of Target of Rapamycin (TOR), and a dramatic accumulation of lipid droplets (LDs). Pharmacologic or genetic enhancement of lipid utilization by the mitochondria decreased LD accumulation, attenuated TOR activation and rescued GSC loss caused by inhibition of mitochondrial fusion. However, the mechanism(s) leading to GSC loss were unclear. TOR activation has been demonstrated to suppress JAK-STAT signaling by stabilizing the JAK-STAT inhibitor SOCS36E. As JAK-STAT signaling is critical for regulating stem cell self-renewal in the testis, we wanted to test the hypothesis that the increase in TOR activity in early germ cells would lead to SOCS36E stabilization, which in turn, could contribute to stem cell loss.  Indeed, we found that SOCS36E levels were higher in early germ cells upon depletion of dMfn or Opa1. Subsequently, we show that activation of the JAK-STAT pathway, but not BMP signaling, is sufficient to rescue loss of GSCs as a result of the block in mitochondrial fusion.  In addition, preliminary genetic and proximity-labeling data suggest that LD accumulation acts in parallel to TOR/SOCS36E to promote GSC loss. Our findings highlight a critical role for mitochondrial metabolism and lipid homeostasis in GSC maintenance, providing a framework for investigating the impact of metabolic diseases on stem cell function and tissue homeostasis.

Dr. Rafael Demarco | Demarco Lab

Bio:

I am a new Assistant Professor in the Department of Biology at the University of Louisville whose ultimate goal is to understand how changes in metabolism impact stem cell behavior during homeostasis, aging and stress conditions. I was trained as a geneticist during my Ph.D. with Dr. Erik Lundquist at the University of Kansas, where I learned to ask questions and interpret genetic data using model organisms. To pursue my objective of studying stem cells and their niches, I obtained my postdoctoral training and later position as a Research Specialist in the laboratory of Dr. Leanne Jones (first at the Salk Institute and then at the University of California, Los Angeles and San Francisco), a leading expert in the fields of stem cells and current director of the Bakar Aging Research Institute at UCSF. During my time working with Dr. Jones, I developed my own research interests focusing on how different aspects of metabolism impact the stem cell niche present in the Drosophila testis. Unexpectedly, I found that both stem cell populations present in the testis niche employ mechanisms to maintain proper lipid homeostasis in order to prevent stem cell loss. Disruptions in either mitochondrial fusion (in germline stem cells1) or autophagy (in cyst stem cells2) led to deficient lipid catabolism and ectopic accumulation of lipids in the stem cell niche, which promoted stem cell loss through differentiation. Hence, a model has emerged revealing a novel metabolic facet in the regulation of stem cell fate, which appears conserved across stem cell systems3. In my recently established laboratory, I am engaged in pursuing the mechanism(s) through which ectopic lipid accumulation can impact stem cell fate within the niche, which could shed light into the development of new strategies targeting stem cell-based regenerative therapies.

Abstract:

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for male germline stem cell (GSC) maintenance in Drosophila melanogaster.  Depletion of Mitofusin (dMfn) or Optic atrophy 1 (Opa1) led to dysfunctional mitochondria, activation of Target of Rapamycin (TOR), and a dramatic accumulation of lipid droplets (LDs). Pharmacologic or genetic enhancement of lipid utilization by the mitochondria decreased LD accumulation, attenuated TOR activation and rescued GSC loss caused by inhibition of mitochondrial fusion. However, the mechanism(s) leading to GSC loss were unclear. TOR activation has been demonstrated to suppress JAK-STAT signaling by stabilizing the JAK-STAT inhibitor SOCS36E. As JAK-STAT signaling is critical for regulating stem cell self-renewal in the testis, we wanted to test the hypothesis that the increase in TOR activity in early germ cells would lead to SOCS36E stabilization, which in turn, could contribute to stem cell loss.  Indeed, we found that SOCS36E levels were higher in early germ cells upon depletion of dMfn or Opa1. Subsequently, we show that activation of the JAK-STAT pathway, but not BMP signaling, is sufficient to rescue loss of GSCs as a result of the block in mitochondrial fusion.  In addition, preliminary genetic and proximity-labeling data suggest that LD accumulation acts in parallel to TOR/SOCS36E to promote GSC loss. Our findings highlight a critical role for mitochondrial metabolism and lipid homeostasis in GSC maintenance, providing a framework for investigating the impact of metabolic diseases on stem cell function and tissue homeostasis.

Dr. Rafael Demarco | Demarco Lab

Bio:

I am a new Assistant Professor in the Department of Biology at the University of Louisville whose ultimate goal is to understand how changes in metabolism impact stem cell behavior during homeostasis, aging and stress conditions. I was trained as a geneticist during my Ph.D. with Dr. Erik Lundquist at the University of Kansas, where I learned to ask questions and interpret genetic data using model organisms. To pursue my objective of studying stem cells and their niches, I obtained my postdoctoral training and later position as a Research Specialist in the laboratory of Dr. Leanne Jones (first at the Salk Institute and then at the University of California, Los Angeles and San Francisco), a leading expert in the fields of stem cells and current director of the Bakar Aging Research Institute at UCSF. During my time working with Dr. Jones, I developed my own research interests focusing on how different aspects of metabolism impact the stem cell niche present in the Drosophila testis. Unexpectedly, I found that both stem cell populations present in the testis niche employ mechanisms to maintain proper lipid homeostasis in order to prevent stem cell loss. Disruptions in either mitochondrial fusion (in germline stem cells1) or autophagy (in cyst stem cells2) led to deficient lipid catabolism and ectopic accumulation of lipids in the stem cell niche, which promoted stem cell loss through differentiation. Hence, a model has emerged revealing a novel metabolic facet in the regulation of stem cell fate, which appears conserved across stem cell systems3. In my recently established laboratory, I am engaged in pursuing the mechanism(s) through which ectopic lipid accumulation can impact stem cell fate within the niche, which could shed light into the development of new strategies targeting stem cell-based regenerative therapies.

Abstract:

The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. A genetic screen targeting regulators of mitochondrial dynamics revealed that mitochondrial fusion is required for male germline stem cell (GSC) maintenance in Drosophila melanogaster.  Depletion of Mitofusin (dMfn) or Optic atrophy 1 (Opa1) led to dysfunctional mitochondria, activation of Target of Rapamycin (TOR), and a dramatic accumulation of lipid droplets (LDs). Pharmacologic or genetic enhancement of lipid utilization by the mitochondria decreased LD accumulation, attenuated TOR activation and rescued GSC loss caused by inhibition of mitochondrial fusion. However, the mechanism(s) leading to GSC loss were unclear. TOR activation has been demonstrated to suppress JAK-STAT signaling by stabilizing the JAK-STAT inhibitor SOCS36E. As JAK-STAT signaling is critical for regulating stem cell self-renewal in the testis, we wanted to test the hypothesis that the increase in TOR activity in early germ cells would lead to SOCS36E stabilization, which in turn, could contribute to stem cell loss.  Indeed, we found that SOCS36E levels were higher in early germ cells upon depletion of dMfn or Opa1. Subsequently, we show that activation of the JAK-STAT pathway, but not BMP signaling, is sufficient to rescue loss of GSCs as a result of the block in mitochondrial fusion.  In addition, preliminary genetic and proximity-labeling data suggest that LD accumulation acts in parallel to TOR/SOCS36E to promote GSC loss. Our findings highlight a critical role for mitochondrial metabolism and lipid homeostasis in GSC maintenance, providing a framework for investigating the impact of metabolic diseases on stem cell function and tissue homeostasis.

Dr. Jessica Blois | Blois Lab

BIO:

Dr. Jessica Blois is an Associate Professor in the Department of Life and Environmental Sciences at UC Merced. Her research is particularly focused on examining the relative roles of environmental versus biotic drivers of biodiversity change, in merging data from different kinds of fossil proxies such as mammal bones and plant macrofossils, and in applying perspectives from the past to help conserve biodiversity. Her work combines field work aimed at broadening our samples of fossil and modern mammals, phylogeographic analyses to understand how genetic diversity is structured spatiotemporally, and paleobiogeographic modeling. Dr. Blois’ primary study system is North American mammals from the past 21,000 years, and she also has a strong focus on developing the paleo-informatic infrastructure to enable large-scale science.

Abstract:

Climates today are changing substantially and will continue to do so over the next hundred years and beyond. All of the different elements that comprise Earth’s biosphere—its biodiversity—depend on and respond to Earth’s climate in a variety of ways, and in turn, Earth’s biodiversity modulates the magnitude and trajectory of climate change. Species responses to highly novel climatic (and other anthropogenically-forced) conditions—which may fall outside the range of conditions experienced by species over their histories—will impact the adaptive capacity and evolutionary potential of species and shape future patterns of biodiversity. In this talk, I will present several recent projects illustrating how climate impacts biodiversity. I will focus on ecological processes that structure local populations and communities, and then move towards how we can scale up towards a broader understanding of how ecological processes structure biodiversity patterns across space and time.

Watch the seminar here!

Dr. Jessica Blois | Blois Lab

BIO:

Dr. Jessica Blois is an Associate Professor in the Department of Life and Environmental Sciences at UC Merced. Her research is particularly focused on examining the relative roles of environmental versus biotic drivers of biodiversity change, in merging data from different kinds of fossil proxies such as mammal bones and plant macrofossils, and in applying perspectives from the past to help conserve biodiversity. Her work combines field work aimed at broadening our samples of fossil and modern mammals, phylogeographic analyses to understand how genetic diversity is structured spatiotemporally, and paleobiogeographic modeling. Dr. Blois’ primary study system is North American mammals from the past 21,000 years, and she also has a strong focus on developing the paleo-informatic infrastructure to enable large-scale science.

Abstract:

Climates today are changing substantially and will continue to do so over the next hundred years and beyond. All of the different elements that comprise Earth’s biosphere—its biodiversity—depend on and respond to Earth’s climate in a variety of ways, and in turn, Earth’s biodiversity modulates the magnitude and trajectory of climate change. Species responses to highly novel climatic (and other anthropogenically-forced) conditions—which may fall outside the range of conditions experienced by species over their histories—will impact the adaptive capacity and evolutionary potential of species and shape future patterns of biodiversity. In this talk, I will present several recent projects illustrating how climate impacts biodiversity. I will focus on ecological processes that structure local populations and communities, and then move towards how we can scale up towards a broader understanding of how ecological processes structure biodiversity patterns across space and time.

Watch the seminar here!

Dr. Jessica Blois | Blois Lab

BIO:

Dr. Jessica Blois is an Associate Professor in the Department of Life and Environmental Sciences at UC Merced. Her research is particularly focused on examining the relative roles of environmental versus biotic drivers of biodiversity change, in merging data from different kinds of fossil proxies such as mammal bones and plant macrofossils, and in applying perspectives from the past to help conserve biodiversity. Her work combines field work aimed at broadening our samples of fossil and modern mammals, phylogeographic analyses to understand how genetic diversity is structured spatiotemporally, and paleobiogeographic modeling. Dr. Blois’ primary study system is North American mammals from the past 21,000 years, and she also has a strong focus on developing the paleo-informatic infrastructure to enable large-scale science.

Abstract:

Climates today are changing substantially and will continue to do so over the next hundred years and beyond. All of the different elements that comprise Earth’s biosphere—its biodiversity—depend on and respond to Earth’s climate in a variety of ways, and in turn, Earth’s biodiversity modulates the magnitude and trajectory of climate change. Species responses to highly novel climatic (and other anthropogenically-forced) conditions—which may fall outside the range of conditions experienced by species over their histories—will impact the adaptive capacity and evolutionary potential of species and shape future patterns of biodiversity. In this talk, I will present several recent projects illustrating how climate impacts biodiversity. I will focus on ecological processes that structure local populations and communities, and then move towards how we can scale up towards a broader understanding of how ecological processes structure biodiversity patterns across space and time.

Watch the seminar here!

Dr. Jessica Blois | Blois Lab

BIO:

Dr. Jessica Blois is an Associate Professor in the Department of Life and Environmental Sciences at UC Merced. Her research is particularly focused on examining the relative roles of environmental versus biotic drivers of biodiversity change, in merging data from different kinds of fossil proxies such as mammal bones and plant macrofossils, and in applying perspectives from the past to help conserve biodiversity. Her work combines field work aimed at broadening our samples of fossil and modern mammals, phylogeographic analyses to understand how genetic diversity is structured spatiotemporally, and paleobiogeographic modeling. Dr. Blois’ primary study system is North American mammals from the past 21,000 years, and she also has a strong focus on developing the paleo-informatic infrastructure to enable large-scale science.

Abstract:

Climates today are changing substantially and will continue to do so over the next hundred years and beyond. All of the different elements that comprise Earth’s biosphere—its biodiversity—depend on and respond to Earth’s climate in a variety of ways, and in turn, Earth’s biodiversity modulates the magnitude and trajectory of climate change. Species responses to highly novel climatic (and other anthropogenically-forced) conditions—which may fall outside the range of conditions experienced by species over their histories—will impact the adaptive capacity and evolutionary potential of species and shape future patterns of biodiversity. In this talk, I will present several recent projects illustrating how climate impacts biodiversity. I will focus on ecological processes that structure local populations and communities, and then move towards how we can scale up towards a broader understanding of how ecological processes structure biodiversity patterns across space and time.

Watch the seminar here!

Hugo Reyes-Centeno HEVA (Human Evolution & Virtual Anthropology Lab) EduceLab

Dr. Hugo Reyes-Centeno is an evolutionary anthropologist specializing on the emergence of modern human anatomy and behavior over the last million years. In addition, he conducts inter-disciplinary research on human biocultural diversity and the study of natural and cultural heritage worldwide. Prior to joining the University of Kentucky in 2020 as Assistant Professor of Anthropology, he served as Scientific Coordinator and co-founder of the Center for Advanced Studies “Words, Bones, Genes, Tools” at the University of Tübingen (Germany), where he also completed a dissertation in the Institute of Archaeological Science and the Senckenberg Centre for Human Evolution and Paleoenvironments. His research has appeared in Cell, PNAS, Journal of Human Evolution, and PLoS Genetics, among other venues. He has performed paleontological and archaeological fieldwork in France, Italy, Peru, the Philippines, and Spain. Currently, he serves as Co-PI of the NSF-funded EduceLab: Infrastructure for Next Generation Heritage Science.

Abstract: Despite consensus on the emergence of anatomically modern humans in Africa and their subsequent dispersal into the rest of the world, the mode and timing of these processes remain controversial topics. In addressing them, data on human anatomical and genomic variation have sometimes generated conflicting inferences. Therefore, approaches that consider both lines of evidence under a common theoretical framework are important for reconciling competing evolutionary models. In this talk, I highlight research that tests competing models of human dispersal out of Africa, which applies quantitative genetic and population genetic methods to anatomical and genomic data. I discuss the caveats of these conclusions, including the influence of admixture between modern humans and other hominins. Furthermore, I examine how these findings align with the known human fossil record and a growing inventory of ancient genomes from archaeological and paleontological contexts. Finally, I review how ongoing field and laboratory projects in Eastern Africa, Southeast Asia, and South America shed light on human evolution, adaptations, and dispersals.