Dr. Deb Bell-Pedersen | Pedersen Lab

Abstract:
The circadian clock is a fundamental regulator of human health and drug metabolism, coordinating daily rhythms in protein production that affect cellular function and metabolism. Many proteins that cycle robustly are produced from nonrhythmic mRNAs, pointing to translational control as a key mechanism of rhythmic protein levels. Using the model eukaryote Neurospora crassa, we discovered that the clock exerts this regulation through rhythmic control of a conserved translation initiation factor (eIF2α) and by remodeling ribosome composition. Even more unexpectedly, we discovered that the circadian system governs the fidelity of protein synthesis by modulating ribosome makeup and tRNA synthetase activity. Both translational fidelity and circadian amplitude decline with age. We identified compounds that restore clock amplitude in old N. crassa cells, leading to improved translation accuracy and extended lifespan. These findings reveal how the circadian clock programs daily changes in the proteome beyond genomic instructions and highlight a novel link among circadian regulation, proteome integrity and aging.

Dr. Deb Bell-Pedersen | Pedersen Lab

Abstract:
The circadian clock is a fundamental regulator of human health and drug metabolism, coordinating daily rhythms in protein production that affect cellular function and metabolism. Many proteins that cycle robustly are produced from nonrhythmic mRNAs, pointing to translational control as a key mechanism of rhythmic protein levels. Using the model eukaryote Neurospora crassa, we discovered that the clock exerts this regulation through rhythmic control of a conserved translation initiation factor (eIF2α) and by remodeling ribosome composition. Even more unexpectedly, we discovered that the circadian system governs the fidelity of protein synthesis by modulating ribosome makeup and tRNA synthetase activity. Both translational fidelity and circadian amplitude decline with age. We identified compounds that restore clock amplitude in old N. crassa cells, leading to improved translation accuracy and extended lifespan. These findings reveal how the circadian clock programs daily changes in the proteome beyond genomic instructions and highlight a novel link among circadian regulation, proteome integrity and aging.

Dr. Deb Bell-Pedersen | Pedersen Lab

Abstract:
The circadian clock is a fundamental regulator of human health and drug metabolism, coordinating daily rhythms in protein production that affect cellular function and metabolism. Many proteins that cycle robustly are produced from nonrhythmic mRNAs, pointing to translational control as a key mechanism of rhythmic protein levels. Using the model eukaryote Neurospora crassa, we discovered that the clock exerts this regulation through rhythmic control of a conserved translation initiation factor (eIF2α) and by remodeling ribosome composition. Even more unexpectedly, we discovered that the circadian system governs the fidelity of protein synthesis by modulating ribosome makeup and tRNA synthetase activity. Both translational fidelity and circadian amplitude decline with age. We identified compounds that restore clock amplitude in old N. crassa cells, leading to improved translation accuracy and extended lifespan. These findings reveal how the circadian clock programs daily changes in the proteome beyond genomic instructions and highlight a novel link among circadian regulation, proteome integrity and aging.

Alejandro Sánchez Alvarado | Sánchez Alvarado Lab

Bio:
Sánchez Alvarado received a B.S. in molecular biology and chemistry from Vanderbilt University in Nashville, Tennessee, and a Ph.D. in pharmacology and cell biophysics from the University of Cincinnati College of Medicine. He performed postdoctoral and independent research at the Carnegie Institution of Washington, Department of Embryology in Baltimore. In 2002, he joined the faculty of the University of Utah School of Medicine in Salt Lake City, where he held the H.A. & Edna Benning Presidential Endowed Chair. In 2005, he was named a Howard Hughes Medical Institute investigator. He joined the Stowers Institute for Medical Research in Kansas City in 2011 and became the president and chief scientific officer of the Stowers Institute in 2022. He also holds the Priscilla Wood Neaves Chair in the Biomedical Sciences.

Sánchez Alvarado is an elected member of the National Academy of Science, the American Academy of Arts and Sciences and the Latin American Academy of Sciences; a Kavli Fellow of the National Academy of Sciences USA; a fellow of the Marine Biological Laboratory in Woods Hole, MA; a fellow of the American Association for the Advancement of Science; and a recipient of a National Institutes of Health MERIT award, the EE Just Medal for Scientific Achievement and the Vilcek Prize in Biomedical Sciences. He has served on numerous scientific advisory committees and boards including the National Advisory Council of the National Institute of General Medical Sciences and the National Institutes of Health. He serves on the Board of Directors of American Century Investments.

Sánchez Alvarado’s work has the potential to lead to a better understanding of how the adult forms of higher organisms, including humans, carry out their biological functions. His research also has led to insights on the molecular and genetic drivers of both regenerative and degenerative cellular processes that contribute to disease.

Abstract:
It is paradoxical that for many organisms (including humans), the apparent anatomical stability of their adult bodies is maintained by constant change. Despite the importance of tissue homeostasis and regeneration to human biology and health, relatively little is known about how these processes are regulated. As such, numerous questions remain, including: 

• How do organ systems maintain their order and function while in a state of cell flux?
• How do animals control and coordinate the size and cell number of multiple organ systems?
• Does regeneration of body parts lost to injury invoke embryonic processes, generic patterning mechanisms or unique circuitry comprised of well-established patterning genes? 

Answering any of these questions would set a baseline from which to try to enhance regenerative properties in multicellular organisms such as humans, particularly after injury.

One way to solve a complex problem is to reduce it to a simpler, easier way to answer problem. Therefore, reducing the complexities of regeneration and tissue homeostasis to the study of comparatively simpler systems would allow for a systematic dissection and mechanistic understanding of these processes. Here, I will discuss how the use of single-cell and spatial transcriptomics is helping define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarian Schmidtea mediterranea and regeneration of missing organs in the hemichordate Ptychodera flava. Our studies are beginning to shed light on the way adult animals regulate tissue homeostasis and the replacement of body parts lost to injury.

Watch the seminar here!

Alejandro Sánchez Alvarado | Sánchez Alvarado Lab

Bio:
Sánchez Alvarado received a B.S. in molecular biology and chemistry from Vanderbilt University in Nashville, Tennessee, and a Ph.D. in pharmacology and cell biophysics from the University of Cincinnati College of Medicine. He performed postdoctoral and independent research at the Carnegie Institution of Washington, Department of Embryology in Baltimore. In 2002, he joined the faculty of the University of Utah School of Medicine in Salt Lake City, where he held the H.A. & Edna Benning Presidential Endowed Chair. In 2005, he was named a Howard Hughes Medical Institute investigator. He joined the Stowers Institute for Medical Research in Kansas City in 2011 and became the president and chief scientific officer of the Stowers Institute in 2022. He also holds the Priscilla Wood Neaves Chair in the Biomedical Sciences.

Sánchez Alvarado is an elected member of the National Academy of Science, the American Academy of Arts and Sciences and the Latin American Academy of Sciences; a Kavli Fellow of the National Academy of Sciences USA; a fellow of the Marine Biological Laboratory in Woods Hole, MA; a fellow of the American Association for the Advancement of Science; and a recipient of a National Institutes of Health MERIT award, the EE Just Medal for Scientific Achievement and the Vilcek Prize in Biomedical Sciences. He has served on numerous scientific advisory committees and boards including the National Advisory Council of the National Institute of General Medical Sciences and the National Institutes of Health. He serves on the Board of Directors of American Century Investments.

Sánchez Alvarado’s work has the potential to lead to a better understanding of how the adult forms of higher organisms, including humans, carry out their biological functions. His research also has led to insights on the molecular and genetic drivers of both regenerative and degenerative cellular processes that contribute to disease.

Abstract:
It is paradoxical that for many organisms (including humans), the apparent anatomical stability of their adult bodies is maintained by constant change. Despite the importance of tissue homeostasis and regeneration to human biology and health, relatively little is known about how these processes are regulated. As such, numerous questions remain, including: 

• How do organ systems maintain their order and function while in a state of cell flux?
• How do animals control and coordinate the size and cell number of multiple organ systems?
• Does regeneration of body parts lost to injury invoke embryonic processes, generic patterning mechanisms or unique circuitry comprised of well-established patterning genes? 

Answering any of these questions would set a baseline from which to try to enhance regenerative properties in multicellular organisms such as humans, particularly after injury.

One way to solve a complex problem is to reduce it to a simpler, easier way to answer problem. Therefore, reducing the complexities of regeneration and tissue homeostasis to the study of comparatively simpler systems would allow for a systematic dissection and mechanistic understanding of these processes. Here, I will discuss how the use of single-cell and spatial transcriptomics is helping define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarian Schmidtea mediterranea and regeneration of missing organs in the hemichordate Ptychodera flava. Our studies are beginning to shed light on the way adult animals regulate tissue homeostasis and the replacement of body parts lost to injury.

Watch the seminar here!

Alejandro Sánchez Alvarado | Sánchez Alvarado Lab

Bio:
Sánchez Alvarado received a B.S. in molecular biology and chemistry from Vanderbilt University in Nashville, Tennessee, and a Ph.D. in pharmacology and cell biophysics from the University of Cincinnati College of Medicine. He performed postdoctoral and independent research at the Carnegie Institution of Washington, Department of Embryology in Baltimore. In 2002, he joined the faculty of the University of Utah School of Medicine in Salt Lake City, where he held the H.A. & Edna Benning Presidential Endowed Chair. In 2005, he was named a Howard Hughes Medical Institute investigator. He joined the Stowers Institute for Medical Research in Kansas City in 2011 and became the president and chief scientific officer of the Stowers Institute in 2022. He also holds the Priscilla Wood Neaves Chair in the Biomedical Sciences.

Sánchez Alvarado is an elected member of the National Academy of Science, the American Academy of Arts and Sciences and the Latin American Academy of Sciences; a Kavli Fellow of the National Academy of Sciences USA; a fellow of the Marine Biological Laboratory in Woods Hole, MA; a fellow of the American Association for the Advancement of Science; and a recipient of a National Institutes of Health MERIT award, the EE Just Medal for Scientific Achievement and the Vilcek Prize in Biomedical Sciences. He has served on numerous scientific advisory committees and boards including the National Advisory Council of the National Institute of General Medical Sciences and the National Institutes of Health. He serves on the Board of Directors of American Century Investments.

Sánchez Alvarado’s work has the potential to lead to a better understanding of how the adult forms of higher organisms, including humans, carry out their biological functions. His research also has led to insights on the molecular and genetic drivers of both regenerative and degenerative cellular processes that contribute to disease.

Abstract:
It is paradoxical that for many organisms (including humans), the apparent anatomical stability of their adult bodies is maintained by constant change. Despite the importance of tissue homeostasis and regeneration to human biology and health, relatively little is known about how these processes are regulated. As such, numerous questions remain, including: 

• How do organ systems maintain their order and function while in a state of cell flux?
• How do animals control and coordinate the size and cell number of multiple organ systems?
• Does regeneration of body parts lost to injury invoke embryonic processes, generic patterning mechanisms or unique circuitry comprised of well-established patterning genes? 

Answering any of these questions would set a baseline from which to try to enhance regenerative properties in multicellular organisms such as humans, particularly after injury.

One way to solve a complex problem is to reduce it to a simpler, easier way to answer problem. Therefore, reducing the complexities of regeneration and tissue homeostasis to the study of comparatively simpler systems would allow for a systematic dissection and mechanistic understanding of these processes. Here, I will discuss how the use of single-cell and spatial transcriptomics is helping define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarian Schmidtea mediterranea and regeneration of missing organs in the hemichordate Ptychodera flava. Our studies are beginning to shed light on the way adult animals regulate tissue homeostasis and the replacement of body parts lost to injury.

Watch the seminar here!

Alejandro Sánchez Alvarado | Sánchez Alvarado Lab

Bio:
Sánchez Alvarado received a B.S. in molecular biology and chemistry from Vanderbilt University in Nashville, Tennessee, and a Ph.D. in pharmacology and cell biophysics from the University of Cincinnati College of Medicine. He performed postdoctoral and independent research at the Carnegie Institution of Washington, Department of Embryology in Baltimore. In 2002, he joined the faculty of the University of Utah School of Medicine in Salt Lake City, where he held the H.A. & Edna Benning Presidential Endowed Chair. In 2005, he was named a Howard Hughes Medical Institute investigator. He joined the Stowers Institute for Medical Research in Kansas City in 2011 and became the president and chief scientific officer of the Stowers Institute in 2022. He also holds the Priscilla Wood Neaves Chair in the Biomedical Sciences.

Sánchez Alvarado is an elected member of the National Academy of Science, the American Academy of Arts and Sciences and the Latin American Academy of Sciences; a Kavli Fellow of the National Academy of Sciences USA; a fellow of the Marine Biological Laboratory in Woods Hole, MA; a fellow of the American Association for the Advancement of Science; and a recipient of a National Institutes of Health MERIT award, the EE Just Medal for Scientific Achievement and the Vilcek Prize in Biomedical Sciences. He has served on numerous scientific advisory committees and boards including the National Advisory Council of the National Institute of General Medical Sciences and the National Institutes of Health. He serves on the Board of Directors of American Century Investments.

Sánchez Alvarado’s work has the potential to lead to a better understanding of how the adult forms of higher organisms, including humans, carry out their biological functions. His research also has led to insights on the molecular and genetic drivers of both regenerative and degenerative cellular processes that contribute to disease.

Abstract:
It is paradoxical that for many organisms (including humans), the apparent anatomical stability of their adult bodies is maintained by constant change. Despite the importance of tissue homeostasis and regeneration to human biology and health, relatively little is known about how these processes are regulated. As such, numerous questions remain, including: 

• How do organ systems maintain their order and function while in a state of cell flux?
• How do animals control and coordinate the size and cell number of multiple organ systems?
• Does regeneration of body parts lost to injury invoke embryonic processes, generic patterning mechanisms or unique circuitry comprised of well-established patterning genes? 

Answering any of these questions would set a baseline from which to try to enhance regenerative properties in multicellular organisms such as humans, particularly after injury.

One way to solve a complex problem is to reduce it to a simpler, easier way to answer problem. Therefore, reducing the complexities of regeneration and tissue homeostasis to the study of comparatively simpler systems would allow for a systematic dissection and mechanistic understanding of these processes. Here, I will discuss how the use of single-cell and spatial transcriptomics is helping define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarian Schmidtea mediterranea and regeneration of missing organs in the hemichordate Ptychodera flava. Our studies are beginning to shed light on the way adult animals regulate tissue homeostasis and the replacement of body parts lost to injury.

Watch the seminar here!

Dr. Yvon Woappi | Woappi Lab

Bio:
Dr. Yvon Woappi is the Herbert and Florence Irving Assistant Professor of Physiology and Cellular Biophysics, Dermatology, and Biomedical Engineering at Columbia University. His research leverages gene editing and multiomic technologies to uncover how autonomous multicellular orchestration facilitates deep wound repair – a process critical to many conditions including diabetic ulcers and carcinomas. Dr. Woappi earned his Ph.D. as a Grace Jordan McFadden Fellow at the University of South Carolina and completed his postdoctoral training in the Harvard Dermatology Research Training Program at Harvard Medical School. Dr. Woappi’s pioneering early-career research is laying the foundation for synthetic wound regeneration, a systems bioengineering approach that leverages cellular heterogeneity to enhance tissue regeneration.

Abstract:
As the organ most frequently exposed to predatory pressures, the integument has acquired broad functions, including camouflage, thermoregulation, sensory perception, and tissue repair. These roles are executed through a complex interplay of tissue substructures, including several mini-organ appendages (hair follicles, sebaceous glands, arrector pili muscle, and assorted pilosebaceous units) and five central adnexal structures (blood vessels, sensory neurons, collagenous tissues, immune components, and deep fascia), all embedded within three superimposed tissue strata (the epidermis, dermis, and hypodermis). Given this intricate architecture, the healing of deep skin wounds requires a coordinated organ-level response involving varied cell populations originating from virtually all three embryonic germ layers—ectoderm, mesoderm, and endoderm. However, a comprehensive understanding of the cellular and molecular logic orchestrating this crosstissue response in mammals remains incomplete. Here, we present the Organ-Scale Wound Healing Atlases (OWHA), a comprehensive multiomic single-cell and spatial transcriptomic dataset that captures the dynamic microanatomical tissue niches of the mammalian integument during the entire wound healing sequence, including early and late healing phases. By incorporating multi-omics data across all major phases of healing, OWHA uncovered novel emergent healing cell states and their coordinated cell fate decisions uniquely (multilineage crosstalk) executed after injury, and delineated critical tissue trajectories required for eKective healing of deep wounds. Importantly, comparative analysis between human and mouse revealed conserved network between the epithelial and neuro-endothelial vasculature....(Add missing groups in human only found in our multi modal approach) By providing deeper mechanistic insights of mammalian tissue adaptations for injury response, OWHA serves as a valuable resource for understanding the cellular and molecular mechanisms underlying wound healing in the mammalian integument.

Dr. Yvon Woappi | Woappi Lab

Bio:
Dr. Yvon Woappi is the Herbert and Florence Irving Assistant Professor of Physiology and Cellular Biophysics, Dermatology, and Biomedical Engineering at Columbia University. His research leverages gene editing and multiomic technologies to uncover how autonomous multicellular orchestration facilitates deep wound repair – a process critical to many conditions including diabetic ulcers and carcinomas. Dr. Woappi earned his Ph.D. as a Grace Jordan McFadden Fellow at the University of South Carolina and completed his postdoctoral training in the Harvard Dermatology Research Training Program at Harvard Medical School. Dr. Woappi’s pioneering early-career research is laying the foundation for synthetic wound regeneration, a systems bioengineering approach that leverages cellular heterogeneity to enhance tissue regeneration.

Abstract:
As the organ most frequently exposed to predatory pressures, the integument has acquired broad functions, including camouflage, thermoregulation, sensory perception, and tissue repair. These roles are executed through a complex interplay of tissue substructures, including several mini-organ appendages (hair follicles, sebaceous glands, arrector pili muscle, and assorted pilosebaceous units) and five central adnexal structures (blood vessels, sensory neurons, collagenous tissues, immune components, and deep fascia), all embedded within three superimposed tissue strata (the epidermis, dermis, and hypodermis). Given this intricate architecture, the healing of deep skin wounds requires a coordinated organ-level response involving varied cell populations originating from virtually all three embryonic germ layers—ectoderm, mesoderm, and endoderm. However, a comprehensive understanding of the cellular and molecular logic orchestrating this crosstissue response in mammals remains incomplete. Here, we present the Organ-Scale Wound Healing Atlases (OWHA), a comprehensive multiomic single-cell and spatial transcriptomic dataset that captures the dynamic microanatomical tissue niches of the mammalian integument during the entire wound healing sequence, including early and late healing phases. By incorporating multi-omics data across all major phases of healing, OWHA uncovered novel emergent healing cell states and their coordinated cell fate decisions uniquely (multilineage crosstalk) executed after injury, and delineated critical tissue trajectories required for eKective healing of deep wounds. Importantly, comparative analysis between human and mouse revealed conserved network between the epithelial and neuro-endothelial vasculature....(Add missing groups in human only found in our multi modal approach) By providing deeper mechanistic insights of mammalian tissue adaptations for injury response, OWHA serves as a valuable resource for understanding the cellular and molecular mechanisms underlying wound healing in the mammalian integument.

Dr. Yvon Woappi | Woappi Lab

Bio:
Dr. Yvon Woappi is the Herbert and Florence Irving Assistant Professor of Physiology and Cellular Biophysics, Dermatology, and Biomedical Engineering at Columbia University. His research leverages gene editing and multiomic technologies to uncover how autonomous multicellular orchestration facilitates deep wound repair – a process critical to many conditions including diabetic ulcers and carcinomas. Dr. Woappi earned his Ph.D. as a Grace Jordan McFadden Fellow at the University of South Carolina and completed his postdoctoral training in the Harvard Dermatology Research Training Program at Harvard Medical School. Dr. Woappi’s pioneering early-career research is laying the foundation for synthetic wound regeneration, a systems bioengineering approach that leverages cellular heterogeneity to enhance tissue regeneration.

Abstract:
As the organ most frequently exposed to predatory pressures, the integument has acquired broad functions, including camouflage, thermoregulation, sensory perception, and tissue repair. These roles are executed through a complex interplay of tissue substructures, including several mini-organ appendages (hair follicles, sebaceous glands, arrector pili muscle, and assorted pilosebaceous units) and five central adnexal structures (blood vessels, sensory neurons, collagenous tissues, immune components, and deep fascia), all embedded within three superimposed tissue strata (the epidermis, dermis, and hypodermis). Given this intricate architecture, the healing of deep skin wounds requires a coordinated organ-level response involving varied cell populations originating from virtually all three embryonic germ layers—ectoderm, mesoderm, and endoderm. However, a comprehensive understanding of the cellular and molecular logic orchestrating this crosstissue response in mammals remains incomplete. Here, we present the Organ-Scale Wound Healing Atlases (OWHA), a comprehensive multiomic single-cell and spatial transcriptomic dataset that captures the dynamic microanatomical tissue niches of the mammalian integument during the entire wound healing sequence, including early and late healing phases. By incorporating multi-omics data across all major phases of healing, OWHA uncovered novel emergent healing cell states and their coordinated cell fate decisions uniquely (multilineage crosstalk) executed after injury, and delineated critical tissue trajectories required for eKective healing of deep wounds. Importantly, comparative analysis between human and mouse revealed conserved network between the epithelial and neuro-endothelial vasculature....(Add missing groups in human only found in our multi modal approach) By providing deeper mechanistic insights of mammalian tissue adaptations for injury response, OWHA serves as a valuable resource for understanding the cellular and molecular mechanisms underlying wound healing in the mammalian integument.