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Biology department seminar

"Quantitative Proteomics for Understanding Epigenetic Mechanisms in Human Disease"

Garcia Selfie

Dr. Benjamin Garcia | Garcia Lab

Bio: 
Benjamin A. Garcia obtained his BS in Chemistry at UC Davis in 2000, where he worked as an undergraduate researcher in Prof. Carlito Lebrilla’s laboratory. He received his PhD in Chemistry in 2005 at the University of Virginia under Prof. Donald Hunt and then was an NIH NRSA Postdoctoral Fellow at the University of Illinois under Prof. Neil Kelleher from 2005-2008. From there Ben was appointed as an Assistant Professor in the Molecular Biology Department at Princeton University from 2008-2012, until his recruitment as the Presidential Associate Professor of Biochemistry and Biophysics at the University of Pennsylvania Perelman School of Medicine in 2012, promoted to full Professor in 2016, and named the John McCrea Dickson M.D. Presidential Professor in 2017. Ben moved in the summer of 2021 to the Washington University School of Medicine in St. Louis to become the Raymond H. Wittcoff Distinguished Professor and Head of the Department of Biochemistry and Molecular Biophysics. The Garcia lab has been developing and applying novel proteomic approaches and bioinformatics for interrogating protein modifications, especially those involved in epigenetic mechanisms such as histones during human disease, publishing over 400 publications. He is presently an Associate Editor of the Analytical Chemistry, and Mass Spectrometry Reviews journals; and serves on the editorial boards for the Molecular Omics, the Journal of Proteome Research and the Molecular and Cellular Proteomics journals. He also serves on the Board of Directors for the U.S. Human Proteome Organization (HUPO), the HUPO Governing Council/Executive Committee and the Executive Committee of the American Chemical Society (ACS) Analytical Chemistry Division. Ben has been recognized with many honors and awards for his mass spectrometry research including the American Society for Mass Spectrometry (ASMS) Research Award, a National Science Foundation CAREER award, an NIH Director’s New Innovator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), an Alfred P. Sloan Fellowship, the PITTCON Achievement Award, the Ken Standing Award, the ACS Arthur F. Findeis Award, The Protein Society Young Investigator Award, the ASMS Biemann Medal, the HUPO Discovery in Proteomic Sciences Award, the Eastern Analytical Symposium (EAS) Outstanding Achievement in Mass Spectrometry Award and was named a Fellow of the Royal Society of Chemistry.

Abstract:
Histones are small proteins that package DNA into chromosomes, and a large number of studies have showed that several post-translational modification (PTM) sites on the histones are associated with both gene activation and silencing.  Along with DNA and small non-coding RNA, histone PTMs make up epigenetic mechanisms that control gene expression patterns outside of DNA sequence mutations. Dysregulation of these chromatin networks underlie several human diseases such as cancer. Here I will give an update on technology advancements that have allowed for high-throughput quantitative mass spectrometry analyses of histone PTMs and chromatin structure, and how we are applying these methods to understand epigenetic reprogramming found in malignant peripheral nerve sheath tumors (MPNSTs). MPNST is an aggressive sarcoma with recurrent loss of function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying complex involved in transcriptional silencing.

Date:
Location:
THM 116

"Quantitative Proteomics for Understanding Epigenetic Mechanisms in Human Disease"

Garcia Selfie

Dr. Benjamin Garcia | Garcia Lab

Bio: 
Benjamin A. Garcia obtained his BS in Chemistry at UC Davis in 2000, where he worked as an undergraduate researcher in Prof. Carlito Lebrilla’s laboratory. He received his PhD in Chemistry in 2005 at the University of Virginia under Prof. Donald Hunt and then was an NIH NRSA Postdoctoral Fellow at the University of Illinois under Prof. Neil Kelleher from 2005-2008. From there Ben was appointed as an Assistant Professor in the Molecular Biology Department at Princeton University from 2008-2012, until his recruitment as the Presidential Associate Professor of Biochemistry and Biophysics at the University of Pennsylvania Perelman School of Medicine in 2012, promoted to full Professor in 2016, and named the John McCrea Dickson M.D. Presidential Professor in 2017. Ben moved in the summer of 2021 to the Washington University School of Medicine in St. Louis to become the Raymond H. Wittcoff Distinguished Professor and Head of the Department of Biochemistry and Molecular Biophysics. The Garcia lab has been developing and applying novel proteomic approaches and bioinformatics for interrogating protein modifications, especially those involved in epigenetic mechanisms such as histones during human disease, publishing over 400 publications. He is presently an Associate Editor of the Analytical Chemistry, and Mass Spectrometry Reviews journals; and serves on the editorial boards for the Molecular Omics, the Journal of Proteome Research and the Molecular and Cellular Proteomics journals. He also serves on the Board of Directors for the U.S. Human Proteome Organization (HUPO), the HUPO Governing Council/Executive Committee and the Executive Committee of the American Chemical Society (ACS) Analytical Chemistry Division. Ben has been recognized with many honors and awards for his mass spectrometry research including the American Society for Mass Spectrometry (ASMS) Research Award, a National Science Foundation CAREER award, an NIH Director’s New Innovator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), an Alfred P. Sloan Fellowship, the PITTCON Achievement Award, the Ken Standing Award, the ACS Arthur F. Findeis Award, The Protein Society Young Investigator Award, the ASMS Biemann Medal, the HUPO Discovery in Proteomic Sciences Award, the Eastern Analytical Symposium (EAS) Outstanding Achievement in Mass Spectrometry Award and was named a Fellow of the Royal Society of Chemistry.

Abstract:
Histones are small proteins that package DNA into chromosomes, and a large number of studies have showed that several post-translational modification (PTM) sites on the histones are associated with both gene activation and silencing.  Along with DNA and small non-coding RNA, histone PTMs make up epigenetic mechanisms that control gene expression patterns outside of DNA sequence mutations. Dysregulation of these chromatin networks underlie several human diseases such as cancer. Here I will give an update on technology advancements that have allowed for high-throughput quantitative mass spectrometry analyses of histone PTMs and chromatin structure, and how we are applying these methods to understand epigenetic reprogramming found in malignant peripheral nerve sheath tumors (MPNSTs). MPNST is an aggressive sarcoma with recurrent loss of function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying complex involved in transcriptional silencing.

Date:
Location:
THM 116

"Quantitative Proteomics for Understanding Epigenetic Mechanisms in Human Disease"

Garcia Selfie

Dr. Benjamin Garcia | Garcia Lab

Bio: 
Benjamin A. Garcia obtained his BS in Chemistry at UC Davis in 2000, where he worked as an undergraduate researcher in Prof. Carlito Lebrilla’s laboratory. He received his PhD in Chemistry in 2005 at the University of Virginia under Prof. Donald Hunt and then was an NIH NRSA Postdoctoral Fellow at the University of Illinois under Prof. Neil Kelleher from 2005-2008. From there Ben was appointed as an Assistant Professor in the Molecular Biology Department at Princeton University from 2008-2012, until his recruitment as the Presidential Associate Professor of Biochemistry and Biophysics at the University of Pennsylvania Perelman School of Medicine in 2012, promoted to full Professor in 2016, and named the John McCrea Dickson M.D. Presidential Professor in 2017. Ben moved in the summer of 2021 to the Washington University School of Medicine in St. Louis to become the Raymond H. Wittcoff Distinguished Professor and Head of the Department of Biochemistry and Molecular Biophysics. The Garcia lab has been developing and applying novel proteomic approaches and bioinformatics for interrogating protein modifications, especially those involved in epigenetic mechanisms such as histones during human disease, publishing over 400 publications. He is presently an Associate Editor of the Analytical Chemistry, and Mass Spectrometry Reviews journals; and serves on the editorial boards for the Molecular Omics, the Journal of Proteome Research and the Molecular and Cellular Proteomics journals. He also serves on the Board of Directors for the U.S. Human Proteome Organization (HUPO), the HUPO Governing Council/Executive Committee and the Executive Committee of the American Chemical Society (ACS) Analytical Chemistry Division. Ben has been recognized with many honors and awards for his mass spectrometry research including the American Society for Mass Spectrometry (ASMS) Research Award, a National Science Foundation CAREER award, an NIH Director’s New Innovator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), an Alfred P. Sloan Fellowship, the PITTCON Achievement Award, the Ken Standing Award, the ACS Arthur F. Findeis Award, The Protein Society Young Investigator Award, the ASMS Biemann Medal, the HUPO Discovery in Proteomic Sciences Award, the Eastern Analytical Symposium (EAS) Outstanding Achievement in Mass Spectrometry Award and was named a Fellow of the Royal Society of Chemistry.

Abstract:
Histones are small proteins that package DNA into chromosomes, and a large number of studies have showed that several post-translational modification (PTM) sites on the histones are associated with both gene activation and silencing.  Along with DNA and small non-coding RNA, histone PTMs make up epigenetic mechanisms that control gene expression patterns outside of DNA sequence mutations. Dysregulation of these chromatin networks underlie several human diseases such as cancer. Here I will give an update on technology advancements that have allowed for high-throughput quantitative mass spectrometry analyses of histone PTMs and chromatin structure, and how we are applying these methods to understand epigenetic reprogramming found in malignant peripheral nerve sheath tumors (MPNSTs). MPNST is an aggressive sarcoma with recurrent loss of function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying complex involved in transcriptional silencing.

Date:
Location:
THM 116

"Quantitative Proteomics for Understanding Epigenetic Mechanisms in Human Disease"

Garcia Selfie

Dr. Benjamin Garcia | Garcia Lab

Bio: 
Benjamin A. Garcia obtained his BS in Chemistry at UC Davis in 2000, where he worked as an undergraduate researcher in Prof. Carlito Lebrilla’s laboratory. He received his PhD in Chemistry in 2005 at the University of Virginia under Prof. Donald Hunt and then was an NIH NRSA Postdoctoral Fellow at the University of Illinois under Prof. Neil Kelleher from 2005-2008. From there Ben was appointed as an Assistant Professor in the Molecular Biology Department at Princeton University from 2008-2012, until his recruitment as the Presidential Associate Professor of Biochemistry and Biophysics at the University of Pennsylvania Perelman School of Medicine in 2012, promoted to full Professor in 2016, and named the John McCrea Dickson M.D. Presidential Professor in 2017. Ben moved in the summer of 2021 to the Washington University School of Medicine in St. Louis to become the Raymond H. Wittcoff Distinguished Professor and Head of the Department of Biochemistry and Molecular Biophysics. The Garcia lab has been developing and applying novel proteomic approaches and bioinformatics for interrogating protein modifications, especially those involved in epigenetic mechanisms such as histones during human disease, publishing over 400 publications. He is presently an Associate Editor of the Analytical Chemistry, and Mass Spectrometry Reviews journals; and serves on the editorial boards for the Molecular Omics, the Journal of Proteome Research and the Molecular and Cellular Proteomics journals. He also serves on the Board of Directors for the U.S. Human Proteome Organization (HUPO), the HUPO Governing Council/Executive Committee and the Executive Committee of the American Chemical Society (ACS) Analytical Chemistry Division. Ben has been recognized with many honors and awards for his mass spectrometry research including the American Society for Mass Spectrometry (ASMS) Research Award, a National Science Foundation CAREER award, an NIH Director’s New Innovator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), an Alfred P. Sloan Fellowship, the PITTCON Achievement Award, the Ken Standing Award, the ACS Arthur F. Findeis Award, The Protein Society Young Investigator Award, the ASMS Biemann Medal, the HUPO Discovery in Proteomic Sciences Award, the Eastern Analytical Symposium (EAS) Outstanding Achievement in Mass Spectrometry Award and was named a Fellow of the Royal Society of Chemistry.

Abstract:
Histones are small proteins that package DNA into chromosomes, and a large number of studies have showed that several post-translational modification (PTM) sites on the histones are associated with both gene activation and silencing.  Along with DNA and small non-coding RNA, histone PTMs make up epigenetic mechanisms that control gene expression patterns outside of DNA sequence mutations. Dysregulation of these chromatin networks underlie several human diseases such as cancer. Here I will give an update on technology advancements that have allowed for high-throughput quantitative mass spectrometry analyses of histone PTMs and chromatin structure, and how we are applying these methods to understand epigenetic reprogramming found in malignant peripheral nerve sheath tumors (MPNSTs). MPNST is an aggressive sarcoma with recurrent loss of function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying complex involved in transcriptional silencing.

Date:
Location:
THM 116

"Be Fruitful and Multiply: How Reproductive Capacity Evolves"

Selfie

Dr. Cassandra Extavour | Extavour Lab

Bio
Cassandra Extavour is a native of Toronto, where she attended the University of Toronto Schools and went on to obtain an Honors BSc at the University of Toronto with a specialist in Molecular Genetics and Molecular Biology, a Major in Mathematics and a Minor in Spanish. She obtained her PhD with Antonio Garcia Bellido at the Severo Ochoa Center for Molecular Biology at the Autonomous University of Madrid. She performed postdoctoral work first with Michalis Averof at the Institute for Molecular Biology and Biotechnology in Crete, Greece, and subsequently with Michael Akam at the University of Cambridge. At Cambridge she received a BBSRC Research Grant and became a Research Associate in the Department of Zoology. In 2007 she established her independent laboratory as an Assistant Professor in the Department of Organismic and Evolutionary Biology at Harvard University, where she was promoted to Associate Professor in 2011 and to Full Professor in 2014. In 2021 she became a Howard Hughes Medical Institute Investigator, and was named the Timken Professor of Organismic and Evolutionary Biology and of Molecular and Cellular Biology at Harvard. Click here to read more.

Abstract:
Reproduction is a crucial fitness parameter, essential for species survival and evolution. Despite its importance, there is massive variation in reproductive capacity across animals, even between very closely related species. Moreover, reproductive capacity can be modified by environmental and ecological factors. Our aim is to understand how genetic variation interacts with ecological variation to regulate distinct and reproductive capacities between species, to determine whether and how ecological variation contributes to the evolution of adaptive variation in reproductive capacity. Our approach takes advantage of the fact that in sexually reproducing animals, the number of offspring that an individual can produce is often predicted by the anatomy of the ovary or testis, the sites of gamete production. In female insects, ovaries are subdivided into egg-producing units called ovarioles, which are generated in species-specific numbers during development. Ovariole number, and correspondingly reproductive capacity, can vary by more than four orders of magnitude across insects. I will discuss our findings on the mechanisms of genetic and environmental control of ovariole number in closely and distantly related insect species, and their implications for the broader questions of the genetic and developmental basis of fitness-relevant evolutionary change.

Date:
Location:
THM 116

"Be Fruitful and Multiply: How Reproductive Capacity Evolves"

Selfie

Dr. Cassandra Extavour | Extavour Lab

Bio
Cassandra Extavour is a native of Toronto, where she attended the University of Toronto Schools and went on to obtain an Honors BSc at the University of Toronto with a specialist in Molecular Genetics and Molecular Biology, a Major in Mathematics and a Minor in Spanish. She obtained her PhD with Antonio Garcia Bellido at the Severo Ochoa Center for Molecular Biology at the Autonomous University of Madrid. She performed postdoctoral work first with Michalis Averof at the Institute for Molecular Biology and Biotechnology in Crete, Greece, and subsequently with Michael Akam at the University of Cambridge. At Cambridge she received a BBSRC Research Grant and became a Research Associate in the Department of Zoology. In 2007 she established her independent laboratory as an Assistant Professor in the Department of Organismic and Evolutionary Biology at Harvard University, where she was promoted to Associate Professor in 2011 and to Full Professor in 2014. In 2021 she became a Howard Hughes Medical Institute Investigator, and was named the Timken Professor of Organismic and Evolutionary Biology and of Molecular and Cellular Biology at Harvard. Click here to read more.

Abstract:
Reproduction is a crucial fitness parameter, essential for species survival and evolution. Despite its importance, there is massive variation in reproductive capacity across animals, even between very closely related species. Moreover, reproductive capacity can be modified by environmental and ecological factors. Our aim is to understand how genetic variation interacts with ecological variation to regulate distinct and reproductive capacities between species, to determine whether and how ecological variation contributes to the evolution of adaptive variation in reproductive capacity. Our approach takes advantage of the fact that in sexually reproducing animals, the number of offspring that an individual can produce is often predicted by the anatomy of the ovary or testis, the sites of gamete production. In female insects, ovaries are subdivided into egg-producing units called ovarioles, which are generated in species-specific numbers during development. Ovariole number, and correspondingly reproductive capacity, can vary by more than four orders of magnitude across insects. I will discuss our findings on the mechanisms of genetic and environmental control of ovariole number in closely and distantly related insect species, and their implications for the broader questions of the genetic and developmental basis of fitness-relevant evolutionary change.

Date:
Location:
THM 116

"Be Fruitful and Multiply: How Reproductive Capacity Evolves"

Selfie

Dr. Cassandra Extavour | Extavour Lab

Bio
Cassandra Extavour is a native of Toronto, where she attended the University of Toronto Schools and went on to obtain an Honors BSc at the University of Toronto with a specialist in Molecular Genetics and Molecular Biology, a Major in Mathematics and a Minor in Spanish. She obtained her PhD with Antonio Garcia Bellido at the Severo Ochoa Center for Molecular Biology at the Autonomous University of Madrid. She performed postdoctoral work first with Michalis Averof at the Institute for Molecular Biology and Biotechnology in Crete, Greece, and subsequently with Michael Akam at the University of Cambridge. At Cambridge she received a BBSRC Research Grant and became a Research Associate in the Department of Zoology. In 2007 she established her independent laboratory as an Assistant Professor in the Department of Organismic and Evolutionary Biology at Harvard University, where she was promoted to Associate Professor in 2011 and to Full Professor in 2014. In 2021 she became a Howard Hughes Medical Institute Investigator, and was named the Timken Professor of Organismic and Evolutionary Biology and of Molecular and Cellular Biology at Harvard. Click here to read more.

Abstract:
Reproduction is a crucial fitness parameter, essential for species survival and evolution. Despite its importance, there is massive variation in reproductive capacity across animals, even between very closely related species. Moreover, reproductive capacity can be modified by environmental and ecological factors. Our aim is to understand how genetic variation interacts with ecological variation to regulate distinct and reproductive capacities between species, to determine whether and how ecological variation contributes to the evolution of adaptive variation in reproductive capacity. Our approach takes advantage of the fact that in sexually reproducing animals, the number of offspring that an individual can produce is often predicted by the anatomy of the ovary or testis, the sites of gamete production. In female insects, ovaries are subdivided into egg-producing units called ovarioles, which are generated in species-specific numbers during development. Ovariole number, and correspondingly reproductive capacity, can vary by more than four orders of magnitude across insects. I will discuss our findings on the mechanisms of genetic and environmental control of ovariole number in closely and distantly related insect species, and their implications for the broader questions of the genetic and developmental basis of fitness-relevant evolutionary change.

Date:
Location:
THM 116

"Be Fruitful and Multiply: How Reproductive Capacity Evolves"

Selfie

Dr. Cassandra Extavour | Extavour Lab

Bio
Cassandra Extavour is a native of Toronto, where she attended the University of Toronto Schools and went on to obtain an Honors BSc at the University of Toronto with a specialist in Molecular Genetics and Molecular Biology, a Major in Mathematics and a Minor in Spanish. She obtained her PhD with Antonio Garcia Bellido at the Severo Ochoa Center for Molecular Biology at the Autonomous University of Madrid. She performed postdoctoral work first with Michalis Averof at the Institute for Molecular Biology and Biotechnology in Crete, Greece, and subsequently with Michael Akam at the University of Cambridge. At Cambridge she received a BBSRC Research Grant and became a Research Associate in the Department of Zoology. In 2007 she established her independent laboratory as an Assistant Professor in the Department of Organismic and Evolutionary Biology at Harvard University, where she was promoted to Associate Professor in 2011 and to Full Professor in 2014. In 2021 she became a Howard Hughes Medical Institute Investigator, and was named the Timken Professor of Organismic and Evolutionary Biology and of Molecular and Cellular Biology at Harvard. Click here to read more.

Abstract:
Reproduction is a crucial fitness parameter, essential for species survival and evolution. Despite its importance, there is massive variation in reproductive capacity across animals, even between very closely related species. Moreover, reproductive capacity can be modified by environmental and ecological factors. Our aim is to understand how genetic variation interacts with ecological variation to regulate distinct and reproductive capacities between species, to determine whether and how ecological variation contributes to the evolution of adaptive variation in reproductive capacity. Our approach takes advantage of the fact that in sexually reproducing animals, the number of offspring that an individual can produce is often predicted by the anatomy of the ovary or testis, the sites of gamete production. In female insects, ovaries are subdivided into egg-producing units called ovarioles, which are generated in species-specific numbers during development. Ovariole number, and correspondingly reproductive capacity, can vary by more than four orders of magnitude across insects. I will discuss our findings on the mechanisms of genetic and environmental control of ovariole number in closely and distantly related insect species, and their implications for the broader questions of the genetic and developmental basis of fitness-relevant evolutionary change.

Date:
Location:
THM 116

"Be Fruitful and Multiply: How Reproductive Capacity Evolves"

Selfie

Dr. Cassandra Extavour | Extavour Lab

Bio
Cassandra Extavour is a native of Toronto, where she attended the University of Toronto Schools and went on to obtain an Honors BSc at the University of Toronto with a specialist in Molecular Genetics and Molecular Biology, a Major in Mathematics and a Minor in Spanish. She obtained her PhD with Antonio Garcia Bellido at the Severo Ochoa Center for Molecular Biology at the Autonomous University of Madrid. She performed postdoctoral work first with Michalis Averof at the Institute for Molecular Biology and Biotechnology in Crete, Greece, and subsequently with Michael Akam at the University of Cambridge. At Cambridge she received a BBSRC Research Grant and became a Research Associate in the Department of Zoology. In 2007 she established her independent laboratory as an Assistant Professor in the Department of Organismic and Evolutionary Biology at Harvard University, where she was promoted to Associate Professor in 2011 and to Full Professor in 2014. In 2021 she became a Howard Hughes Medical Institute Investigator, and was named the Timken Professor of Organismic and Evolutionary Biology and of Molecular and Cellular Biology at Harvard. Click here to read more.

Abstract:
Reproduction is a crucial fitness parameter, essential for species survival and evolution. Despite its importance, there is massive variation in reproductive capacity across animals, even between very closely related species. Moreover, reproductive capacity can be modified by environmental and ecological factors. Our aim is to understand how genetic variation interacts with ecological variation to regulate distinct and reproductive capacities between species, to determine whether and how ecological variation contributes to the evolution of adaptive variation in reproductive capacity. Our approach takes advantage of the fact that in sexually reproducing animals, the number of offspring that an individual can produce is often predicted by the anatomy of the ovary or testis, the sites of gamete production. In female insects, ovaries are subdivided into egg-producing units called ovarioles, which are generated in species-specific numbers during development. Ovariole number, and correspondingly reproductive capacity, can vary by more than four orders of magnitude across insects. I will discuss our findings on the mechanisms of genetic and environmental control of ovariole number in closely and distantly related insect species, and their implications for the broader questions of the genetic and developmental basis of fitness-relevant evolutionary change.

Date:
Location:
THM 116