All posts by medical

Goldberg elected to National Academy of Sciences – The Source – Washington University in St. Louis – Washington University in St. Louis

May 6, 2022 medical

Daniel E. Goldberg, MD, PhD, a renowned researcher in molecular parasitology at Washington University School of Medicine in St. Louis, has been elected to the National Academy of Sciences. Election to the academy, which was announced May 3, is considered one of the highest honors that can be awarded to a U.S. scientist or engineer.

Goldberg, the David M. and Paula L. Kipnis Distinguished Professor, is a professor in theDivision of Infectious Diseaseswithin theDepartment of Medicine, and a professor of molecular microbiology.

Goldbergs work centers on the biochemistry of the parasite that causes malaria. More specifically, his research focuses on the proteins that are synthesized by the parasite, the enzymes that break down the host red blood cell hemoglobin, and different genes that can be targeted for drug therapy. His research seeks to improve the efficiency of treatment and to prevent initial infection.

Malaria, a life-threatening disease, is caused by a parasite that commonly infects a type of mosquito that then transfers the parasite to people. The World Health Organization estimated that in 2020, 241 million people were infected with malaria; of them, some 627,000 died, most of them children in Africa.

The Goldberg labs work involves a combination of biochemical, genetic, genomic, cell biological and physiological approaches aimed at understanding the biology of this nefarious organism.

Goldberg has served in many roles at the university, including as a past co-director of the Division of Infectious Diseases, director of the Medical Scientist Training Program, and as a member of the executive council of the Division of Biology & Biomedical Sciences.

He is a fellow of the American Association for the Advancement of Science, the American Society of Clinical Investigation, and the American Association of Physicians. His many honors include the American Society for Biochemistry and Molecular Biologys prestigious C.C. and Alice Wang Award in Molecular Parasitology. He also was a Howard Hughes Medical Institute Investigator for 20 years.

Goldberg earned a bachelors degree from Harvard University before receiving his medical degree and doctorate at Washington University. He completed his residency at Brigham and Womens Hospital in Boston, a fellowship in infectious diseases at Washington University and a postdoctoral fellowship at Rockefeller University. He then returned to Washington University, where he was named professor in 1998.

The National Academy of Sciences announced 120 newly elected members in the U.S and 30 international members in recognition of their distinguished and continuing achievements in original research. The total number of active members is now 2,512, and the total number of international members is 517. International associates are nonvoting members of the academy, with citizenship outside the United States.

Washington University School of Medicines 1,700 faculty physicians also are the medical staff ofBarnes-JewishandSt. Louis Childrenshospitals. The School of Medicine is a leader in medical research, teaching and patient care, and currently is No. 4 in research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked toBJC HealthCare.

Originally published by the School of Medicine

Cell Biology

Post-doctoral Fellow, Department of Chemistry job with THE UNIVERSITY OF HONG KONG | 292308 – Times Higher Education

May 6, 2022 medical

Work type: Full-timeDepartment: Department of Chemistry (25200)Categories: Academic-related Staff

Applications are invited for appointment as Post-doctoral Fellow in the Department of Chemistry (Ref.: 512690), to commence as soon as possible for two years, with the possibility of renewal subject to satisfactory performance.

Applicants should possess a Ph.D. degree in Biology or relevant fields, with a strong background in cell biology and molecular biology. They should have fluency in written and spoken English and Chinese, a strong sense of responsibility, good organizational skills, leadership skills, the ability to work independently and be self-motivated. The appointee will work on the research area of cell biology under the supervision of Dr. Haibo Jiang. Enquiries about the duties of the post should be sent to Dr. Haibo Jiang at hbjiang@hku.hk.

A highly competitive salary commensurate with qualifications and experience will be offered, in addition to annual leave and medical benefits. At current rates, salaries tax does not exceed 15% of gross income.

The University only accepts online application for the above posts. Applicants should apply online and upload an up-to-date C.V. Review of applications will commence as soon as possible and continue until May 13, 2022, or until the posts are filled, whichever is earlier.

Cell Biology

Five-Year Review of UNC Thurston Arthritis Research Center, Loeser and Archie | Newsroom – UNC Health and UNC School of Medicine

May 6, 2022 medical

An ad hoc committee has been appointed to undertake a routine review of the UNC Thurston Arthritis Research Center and the leadership of Director Richard F. Loeser, Jr., MD, and Joseph P. Archie, Jr., Eminent Professor of Medicine. The review is a standard procedure of the University of North Carolina at Chapel Hill and will take place on June 21, 2022.

The review is a standard procedure of the University of North Carolina at Chapel Hill and will take place on June 21, 2022.

The review committee invites your participation and input:

The deadline to request time on the review committee agenda, or to share written comments, is June 10, 2022.

Note that North Carolina law requires that any written materials developed or received by the committee during the review may be made available to the person reviewed upon request. All requests from the person reviewed will be handled by the Legal Department and any identifying information will be redacted prior to release of the material.

Members of the Review Committee

Mark Zylka, PhD Review Committee Chair, Distinguished Professor, Cell Biology and Physiology

Deborah Givens, PT, DPT, PhD, FAPTA Distinguished Professor, Department of Allied Sciences, Division of Physical Therapy

Corrine Keet, MD, PhD Professor, Department of Pediatrics, Division of Pediatric Allergy and Immunology

Yisong Wan, PhD Professor, Department of Microbiology & Immunology

Roland Tisch, PhD Professor, Department of Microbiology & Immunology

Shannelle Campbell, MD, MPH, FACS Assistant Professor, Department of Surgery

Adesola Akinkuotu, MD Assistant Professor, Department of Medicine, Division of Pediatric Surgery

James Sanders, MD Distinguished Professor, Chair, Department of Orthopaedic Surgery

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Five-Year Review of UNC Thurston Arthritis Research Center, Loeser and Archie | Newsroom - UNC Health and UNC School of Medicine

Cell Biology

With or without sleep: Sleep neuron activity boosts protective gene expression and safeguards survival – EurekAlert

May 6, 2022 medical

image:Activation of the sleep neuron causes a stress gene expression response in the entire body of the worm, visualized here in red by staining for HSP-12.6, a Heat Shock Protein required for survival. view more

Credit: Anastasios Koutsoumparis

Sleep is an essential process that influences all tissues and systems in our bodies. On a molecular level, sleep induces the expression of genes that help maintain the brain and body. Missing a night of sleep is a tremendous challenge to the body. It activates genes that carry out stress response and protect the body from the consequences of sleep deprivation. Part of this stress response is activation of protective genes from the so-called FOXO pathway. This pathway is involved in a multitude of cellular processes that overall contribute to recovery, survival, and longevity. How sleep and lack of sleep trigger these changes in gene expression was not understood. To address this long-standing question, scientists at the Biotechnology Center (BIOTEC) of TU Dresden led by Prof. Henrik Bringmann studied sleep in C. elegans worms.

To trigger sleep, our body has to turn off wakefulness. There is a special set of sleep neurons for this task. These sleep neurons send signals that shut down other neurons responsible for arousal, and in this way promote sleep. Humans have thousands of these sleep neurons located in various centers in the brain, says Prof. Henrik Bringmann. What makes C. elegans a wonderful minimal model to study sleep is that it has only one key sleep-active neuron that induces sleep.

Its All About the Sleep Neuron

The Bringmann team wanted to test how this sleep neuron affects changes in gene expression during sleep. Sleep neurons are active during sleep, and they are activated even further during sleep deprivation. This might be counterintuitive at first but it is because our body acts as a homeostat. If something throws it off balance, our body tries to compensate to restore equilibrium. In this case, disturbing sleep causes the body to activate sleep neurons more and more, in an attempt to force sleep, explains Prof. Bringmann.

The team has genetically engineered two versions of the C. elegans worms. One type had its sleep neuron permanently inactive and the other permanently active. Both of these extreme situations resulted in the loss of sleep. This was an experimental advantage for us, as we were able to test whether the sleep neuron controls gene expression independently of sleep, says Prof. Bringmann.

As a result, scientists observed that the expression of stress response and protective genes decreased when sleep neuron was off. On the other hand, the expression of these genes increased when the sleep neuron was permanently active. These results show that the protective gene expression is a function of sleep neuron activity, explains Prof. Bringmann.

The results provide a new interpretation of the consequences of disturbing sleep in C. elegans. Our experiments suggest that the protective gene expression response that is observed when sleep is disturbed is rather not caused by the actual loss of sleep, but by the overactivation of the sleep neuron, says Prof. Bringmann.

Lessons From The Worm

The results provide an unexpected link between sleep neuron activity and gene expression. While the results originate from the C. elegans worm, they present a potential paradigm shift for understanding the consequences of sleep deprivation and insomnia also in other animals.

Disturbing sleep is known to cause overactivation of sleep-active neurons in many animals, adds Prof. Bringmann. It could be that the activity of sleep neurons controls stress response and the protective, longevity-related gene expression also in other animals and perhaps even in humans. These questions make for an interesting topic of further studies.

Original PublicationAnastasios Koutsoumparis, Luisa M.Welp, Alexander Wulf, Henning Urlaub, David Meierhofer, Stefan Brno, Bernd Timmermann, InkaBusac, Henrik Bringmann: Sleep neuron depolarization promotes protective gene expression changes and FOXO activation. Current Biology (May 2022)Link: https://doi.org/10.1016/j.cub.2022.04.012

About the Biotechnology Center (BIOTEC)The Biotechnology Center (BIOTEC) was founded in 2000 as a central scientific unit of the TU Dresden with the goal of combining modern approaches in molecular and cell biology with the traditionally strong engineering in Dresden. Since 2016, the BIOTEC is part of the central scientific unit Center for Molecular and Cellular Bioengineering (CMCB) of the TU Dresden. The BIOTEC is fostering developments in research and teaching within the Molecular Bioengineering research field and combines approaches in cell biology, biophysics and bioinformatics. It plays a central role within the research priority area Health Sciences, Biomedicine and Bioengineering of the TU Dresden.www.tu-dresden.de/cmcb/biotecwww.tu-dresden.de/cmcb

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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With or without sleep: Sleep neuron activity boosts protective gene expression and safeguards survival - EurekAlert

Cell Biology

CERo Therapeutics’ Multifunctional CER T Cells Synergize with Standard-of-Care Small Molecule Anti-Tumor Inhibitors Across Hematologic and Solid Tumor…

May 6, 2022 medical

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--CERo Therapeutics, Inc., a biopharmaceutical company pioneering the development of novel autologous engineered immune cell therapies, today announced new preclinical data to be presented at the 25th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) demonstrating significant anti-tumor effects of chimeric engulfment receptor (CER) T cells when combined with small molecule therapies in both hematologic and solid tumor models.

CER T cells are multifunctional, genetically engineered T cells that elicit dual cytotoxic and myeloid-like anti-tumor function. CER T-cells, which target a phagocytic ligand that can be induced by small molecules, offer the potential for broad anti-tumor synergisms through a differentiated mechanism of tumor clearance. The data indicate the potential for the unique CER T-cell reprogramming technology to restore immune dysfunction in advanced tumor microenvironments when used in combination with small molecule inhibitors. The differentiated and combined approach offers the potential for more complete and durable responses than targeted agents alone.

Our technology platform reprograms cytotoxic T cells to build in innate immune functions, creating multifunctional CER T cell products that intersect conventional T-cell and myeloid cell-like functions to attack tumors, said Daniel Corey, MD, founder and Chief Scientific Officer of CERo. These data show that CER T cells synergize with current standard-of-care targeted therapies and result in improved tumor clearance and immune activation than either therapy alone in lymphoma and ovarian cancer models. We now have evidence in clinically relevant disease models supporting our approach and look forward to advancing our lead candidate toward IND-enabling studies.

In the ovarian cancer model, CER T cells synergized with sub-clinical doses of the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and niraparib to eliminate tumor cells in vitro. In these studies, the addition of PARP inhibitors drove CER T-cell cytokine and proliferation responses against ovarian cancer cell targets compared to untreated samples. By comparison, CER T cells or PARP inhibitors alone demonstrated minimal anti-tumor function. Synergisms were also observed in mantle cell lymphoma (MCL) models with the Brutons tyrosine kinase inhibitor ibrutinib. The combinatorial approach cleared 90% of tumor cells at sub-therapeutic concentrations of ibrutinib. CER T cells also proliferated and produced T-cell activation cytokines upon target engagement.

Notably, CER T cells exhibited a differentiated mechanism of tumor clearance via enhanced endo/phagocytosis. In co-cultures with MCL tumor cells, CER T cells showed a 15-fold increase in engulfment activity compared to unmodified T cells. Further, in a model system, CER T cells demonstrated the ability to capture, process, and present tumor antigen, and trigger antigen-specific T-cell responses. Finally, in vivo MCL xenograft studies showed that CERs reduced tumor volume relative to controls, with no overt morbidity.

An oral presentation of the abstract entitled Tim-4-Chimeric Engulfment Receptor (CER) T Cell Therapy Elicits Phosphatidylserine-Dependent Cytotoxic and Antigen-Presenting Cell-Like Function and Synergizes with Approved BTK Inhibitors for the Treatment of Hematologic Malignancies (abstract 89) will take place on Monday, May 16, 2022 at 4:45-5:00 p.m. ET during the CAR T-cells and Beyond session in Room 102 A/B.

Data from the poster entitled Tim-4-Chimeric Engulfment Receptor (CER) T Cells Elicit Phosphatidylserine-Dependent Cytotoxic and Innate-Like Function and Synergize with Approved PARP Inhibitors in an Ovarian Cancer Model (abstract 314) will be presented on Monday, May 16.

About CERos Platform TechnologyCERo's technology aims to expand the therapeutic potential of engineered T cell-based therapies by introducing distinct and complementary tumor cell clearance pathways into a single T cell. By engineering T cells to express CERs, CERos platform technology enables T cells to target tumors, induce cellular damage, engulf tumor fragments, and clear tumors, effectively harnessing the anti-tumor attributes of both innate and adaptive immune responses. CER T-cell products are designed to generate a more complete and durable anti-tumor response. This novel biology amends itself to combinations with classic CAR T-cell or small molecule therapy and has potential applications in hematologic malignancies and solid tumors.

About CERo TherapeuticsCERo Therapeutics, Inc. is a biopharmaceutical company pioneering a new class of cell-based therapies that combine attributes of the innate and adaptive arms of the immune system into single T cells. The integrated approach draws on recent advances in synthetic and T-cell biology with the intent to improve upon and optimize cell therapy to increase the curative potential and safety profile of current approaches. CERo is advancing a pipeline of engineered CER T-cell products directed against hematologic malignancies and solid tumors. To learn more about the company and its science, please visit http://www.cero.bio.

Cell Biology

New partnerships, programs and positions are part of Princeton’s ongoing commitment to combat systemic racism – Princeton University

May 6, 2022 medical

An innovative research partnership with the United Negro College Fund and historically Black colleges and universities, the creation of the Effron Center for the Study of America, which embraces diverse and inclusive perspectives on what it means to be American, and a new vice dean position focused on faculty diversity are among Princetons many recent initiatives to address systemic racism.

In summer 2020, President Christopher L. Eisgruber announced a University-wide commitment to combat Americas record of structural inequality and racism as well as Princetons place in that history. Since then, academic and administrative offices have developed action plans to support diversity, equity and inclusion efforts on campus, as well as to help address racial inequities embedded within society.

Princetons efforts have continued and expanded during the current 2021-22 academic year, and an annual report will be published in the fall.

In the meantime, the University is providing an interim update on the projects, programs and partnerships launched so far this year. Of note this spring is the appointment of two new positions at the University:

Princeton published its first annual report in October 2021 highlighting diversity, equity and inclusion work during the 2020-21 academic year. The report also featured demographic and climate data about students, staff, faculty and postdoctoral scholars.

The Universitys diversity, equity and inclusion work has been an ongoing, community-wide process, drawing on the input of hundreds of students, faculty, postdoctoral scholars, staff and alumni, said Michele Minter, vice provost for institutional equity and diversity.

She added that the redoubled efforts of the last two years build on decades of diversity, equity and inclusion work at Princeton.

Moving toward greater diversity, equity and inclusion requires sustained, multigenerational commitment, Minter said. We look forward to working with partners on campus and within higher education on developing new ideas and efforts, and the University will continue to report on our outcomes as this work progresses.

Below is a snapshot of how Princeton has supported its racial equity commitments during the 2021-22 year. The Racial Equity website also includes these updates, as well as more information on the Universitys existing and new diversity and inclusion efforts.

Commitment: Explore the possibility of a new credit- or degree-granting program that would extend Princetons teaching to a new range of students from communities disproportionately affected by systemic racism and other forms of disadvantage.

The Office of the Provost has appointed Cole Crittenden as the inaugural vice provost for academic affairs. Crittenden will identify new opportunities to leverage Princeton's mission, advantages and resources to address the specific needs and aspirations of non-traditional students, with a particular focus on adult learners. The vice provost for academic affairs will work with campus leaders and partner with other institutions serving non-traditional students to seek creative opportunities to support faculty and students at these institutions through collaboration, exchanges and complementary educational experiences and mentoring.

Commitment: Assemble a faculty that more closely reflects both the diverse make-up of Princetons students and the national pool of candidates; establish and strengthen parallel initiatives to diversify the pipeline of Princetons postdoctoral researchers, lecturers, visiting faculty and graduate students; and re-conceive the Faculty Advisory Committee on Diversity.

The Office of the Dean of the Faculty has appointed Frederick Wherry as the inaugural vice dean for diversity and inclusion in the Office of the Dean of the Faculty, and as the director of the Presidential Postdoctoral Research Fellows Program. Wherry will serve as the primary thought leader on matters of diversity and inclusion with respect to all the populations appointed through the Office of the Dean of the Faculty. Twelve scholars from across the disciplines have been named Presidential Postdoctoral Research Fellows for academic year 2021-22. They are the third cohort of fellows appointed at Princeton with the aim of enhancing diversity in the professoriate. The Effron Center for the Study of America was established last November through a major gift to the Venture Forward campaign. For over 75 years, Princetons Program in American Studies has supported teaching and research on America from diverse interdisciplinary perspectives. The Effron Center for the Study of America will enable Princeton to make crucial investments in faculty, visitors and fellows to support emerging areas of American studies scholarship and provide an expanded roster of curricular offerings. Members of the Faculty Advisory Committee on Diversity (FACD) were elected in spring 2021. Chaired by President Eisgruber, the FACD met regularly during the academic year to review and provide feedback on the strategic priorities and planning of senior University academic leaders on diversity and inclusion. The committee also met with the Board of Trustees Committee on Academic Affairs to summarize their efforts and receive feedback from trustees.

Commitment: Develop an institution-wide, multi-year action plan for supplier and contractor diversity.

The Office of Finance and Treasury adopted a multi-year supplier diversity action plan last spring. The plan aims to establish a more diverse supplier base for the University that will broaden the pool of supplier expertise, capabilities and perspectives, and include more businesses that are at least 51% owned and operated by people of color, women, veterans or members of the LGBTQ+ community. An associate director for supplier diversity, Michelle Thomas, has been hired to support the plans implementation. A partnership between Princeton University and the New Jersey Educational Facilities Authority (EFA) will expand opportunities for colleges and universities to invest with diverse asset managers. Approximately $430 million bonds were issued through the EFA and the financing represents the largest transaction in EFA history. Princeton and the EFA plan to continue their groundbreaking partnership creating opportunities for diverse investment banks to participate in future bond issuance. This month, the Office of Facilities convened an action forum of peer institutions, architects, construction leaders and others to explore collaborative strategies for enhancing the pipeline of minority-owned firms in the construction trades.

Commitment: Develop general principles to govern questions about when and under what circumstances it might be appropriate for the University to remove or contextualize the names and representations of historical individuals honored on the Princeton campus.

In April 2021, the Trustee Ad Hoc Committee to Govern Naming and Changes to Campus Iconography released its recommendations for overarching principles for naming, renaming and changing campus iconography. In conjunction with the Trustee Ad Hoc Committees recommendations to continue to diversify and contextualize the visual environment of the campus, Prospect House and sections of Nassau Hall were refreshed with new, community-oriented artwork. This spring, the CPUC Committee on Naming made recommendations to the Board of Trustees regarding additional honorific naming opportunities on campus, which will be announced soon. Three new portraits commissioned in conjunction with the Universitys History and Sense of Place Initiativehave been completed and are scheduled for dedication this month and in the fall. The portraits are of: former U.S. Senator William (Bill) Bradley, Class of 1965; Elaine Fuchs, Graduate School Class of 1977 and a world-renowned leader in cell biology and molecular genetics; and Ruth Simmons, a distinguished Princeton administrator and former vice provost who now serves as president of Prairie View A&M University. The three are among eight new portraits of alumni and former faculty and administrators commissioned since 2018 to reflect the diversity of the University community.

Commitment: Undertake a review of employee policies and benefits with an eye to providing equal access to these benefits for employees in lower-paid positions and others who may have been disproportionally affected by systemic racism or other identity-based inequities.

Enhancements to the Employee Child Care Assistance Program, Childrens Educational Assistance Plan, Long-Term Disability, and Adoption and Surrogacy Program were announced in April. The changes are aimed at promoting greater equity and access to employee benefits, such as doubling the amount that eligible employees may receive to help pay for their childrens college and trade school tuitions and fees.

Commitment: Strengthen support for racial equity and diversity-related professional development and other educational programming. The University organized the Ad Hoc Committee on Racial Equity and Diversity-Related Professional Development, which delivered its report in May 2021. Based on the committees recommendations, Princeton has approved an action plan focused on expansion of training resources and infrastructure. A staff person has been hired to coordinate the implementation of the action plan. The Keller Center launched its inaugural cohort for the Program in Institutional and Historical Racism. The University offered more than 141 professional development workshops and other opportunities to faculty, postdoctoral researchers and staff members during the 2021-22 academic year. These were offered through the Office of Human Resources and the Office of the Vice Provost for Institutional Equity and Diversity, with support from the Office of the Dean of the Faculty.

Commitment: Support academic curricular and scholarly initiatives focused on diversity, equity and inclusion, and addressing systemic racism.

As a part of the Office of the Dean for Researchs Diversity, Equity and Inclusion Action Plan, the Princeton Alliance for Collaborative Research and Innovation (PACRI) was announced this month. PACRI is one of several initiatives aimed at growing a more inclusive research, innovation and entrepreneurship ecosystem at Princeton and beyond. To support the launch of PACRI, Princeton is working with the United Negro College Fund, which has lent its extensive expertise to facilitate the selection of an initial cohort of historically Black colleges and universities (HBCUs) for the pilot phase. The initial partners are: Howard University, Jackson State University, Prairie View A&M University, Spelman College, and the University of Maryland Eastern Shore. The Princeton School of Public and International Affairs (SPIA) announced the appointment of Rayna Truelove as the inaugural associate dean of diversity, equity and inclusion. The newly created role at SPIA reflects the schools efforts to build and sustain an inclusive environment while aligning with the Universitys commitment to diversity and inclusion. The Princeton University Library launched the Early Career Fellowship Programin collaboration with Princetons Office of the Provost and North Carolina Central University School of Library and Information Sciences (NCCU SLIS). The partnership creates eight fellowship opportunities aimed at recent graduates of NCCU SLIS over the course of the next four years. The NCCU SLIS program stands as the only American Library Association-accredited program at an HBCU. Creating a long-term partnership with NCCU SLIS is part of PULs ongoing commitment to implement strategies aimed at recruiting and retaining staff from underrepresented groups. The first two fellows are expected to join PUL this summer, with another two starting in summer 2023. The Program in Linguistics expanded American Sign Language and now allows students to fulfill their language requirement with ASL courses. Princeton also offers the class American Deaf Culture. These courses are part of an expanded focus on disability, accessibility and inclusion across the University, including Princetons physical campus and digital assets, services and programs for students, and new academic programs. Later this month, the Graduate School will host the inaugural Inclusive Academy Symposium. The symposium is an in-person two-day diversity conference focused on supporting graduate students and post-doctoral scholars from underrepresented backgrounds on an array of topics related to success in the academy and on the job market. The symposium will culminate in a dinner recognizing the Best of Access, Diversity and Inclusion, also known as the BADI awards. The BADI awards will honor and celebrate faculty, staff, post-doctoral candidates and graduate students who have made significant impacts in the Princeton graduate student community around diversity and inclusion.

Commitment: Provide increased accountability around institutional goals, and collect and publish additional University data around diversity, equity and inclusion. The inaugural Diversity, Equity and Inclusion annual report, published in October 2021, is available for review or download. The second annual report will be released in fall 2022.

Commitment: Enhance strategies to assure diverse representation and viewpoints on external advisory committees. Over the past two years with the support of the Office of the Dean of the Faculty, the Office of Advancement has worked extensively to begin to build broadly diverse pipelines of accomplished alumni, parents, spouses and friends to recommend for service on advisory councils across disciplines. The Office of Advancement has also engaged academic department chairs to increase partnership on council pipeline development, governance and volunteer management.

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New partnerships, programs and positions are part of Princeton's ongoing commitment to combat systemic racism - Princeton University

Cell Biology

Pathway Discovered That Drives Genomic Changes in Rare Childhood Cancer – Technology Networks

May 6, 2022 medical

In studies using mice grafted with human Ewing sarcoma tissue, researchers from Georgetown University Medical Center and colleagues have identified a biological pathway that is activated when tissue is starved of oxygen due to rapid growth of a tumor, thereby allowing cancer cells to make genetic changes so they can metastasize to the bone and thrive even when exposed to chemotherapy.

The pathway the scientists identified involves a receptor on the surface of a cancer cell, called Y5R, which plays a role in mediating oxygen-deprivation effects if it was blocked or turned off, genetic changes would be limited, thereby inhibiting metastasis of a tumor.

The finding appeared April 28, 2022, inNature Communications.

Each year, about 200 children and young adults in the United States are diagnosed with a Ewing tumor. About half of all Ewing sarcoma diagnoses are in people between the ages of 10 and 20; almost all cases of Ewing sarcoma occur in white and Hispanic people. If the tumor has spread to distant areas at the time of diagnosis, the 5-year survival rate is 38 percent but if it spreads to the bone, survival drops to between 8 and 14 percent.

While the role of rapid genetic changes in spurring the growth of cancer is well known, the mechanisms initiating these changes are not well understood, and strategies to prevent them are lacking, says Joanna Kitlinska, PhD, an associate professor in the Department of Biochemistry and Molecular & Cellular Biology at Georgetown University and corresponding author of the study. Thats why our identification of Y5Rs involvement in initiating such genetic alterations is important, as it gives us a target to aim at or block that could avert cancer genome evolution and resulting progression to metastatic tumors that are resistant to chemotherapy.

The current standard of care for Ewing sarcoma involves systemic cell-killing chemotherapy, which can affect all cells in the body, leading to side effects. There are no treatments targeted at genetic alterations that are used in routine treatment of Ewing sarcoma, which might make treatments less toxic. In particular, adequate treatments for patients with metastatic disease are lacking.

There are currently a number of drugs available that target Y5R because its also implicated in regulating food intake and psychiatric disorders. Several Y5R-targeted drugs have been successfully used in animal studies; one of them was used in human clinical trials for obesity. However, most of them are designed to block functions in the brain that inhibit food intake. According to Kitlinska, the main challenge will be to design Y5R-targeted drugs that do not cross the blood-brain barrier, as these effects are undesirable in cancer patients.

We will keep performing experiments in mice in order to try to identify the mechanisms triggering spread of Ewing to the bone, says Kitlinska. Findings in Ewing sarcoma may also be relevant to other cancer types known to have high expression levels of Y5R, including another pediatric cancer, neuroblastoma, as well as common adulthood malignancies, such as breast, prostate and liver cancers.

Reference:Lu C, Mahajan A, Hong SH, et al. Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma. Nat Commun. 2022;13(1):2323. doi:10.1038/s41467-022-29898-x

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Pathway Discovered That Drives Genomic Changes in Rare Childhood Cancer - Technology Networks

Embryology

Updates to the Human Fertilisation and Embryology (HFE) Act – Lexology

May 6, 2022 medical

On 27 April, the Progress Educational Trust (PET), a charity with the aim of advancing the public understanding of science, law and ethics in the fields of human genetics, assisted reproduction, embryology and stem cell research, ran an online debate on the powers of the Human Fertilisation and Embryology Authority (HFEA).

The session titled 'Authority over Assisted Reproduction: What Powers Should the HFEA Have?', welcomed speakers from across the world of IVF including from the HFEA itself and a patient advocate. Current powers of the HFEA under the HFE Act were discussed, as well as whether these should be extended or pared back in light of the thirty odd years that have gone by since the advent of the HFE Act.

It is clear that the HFEA believes its powers should be expanded to address, among other things, the numerous scientific and technological advances in the area of IVF and the need for sanctions imposed by the HFEA to be proportionate to the specific breaches of the regulations (this would include the power to impose fines). However, several speakers from private clinics voiced their concerns with regard to the clinical expertise of the HFEA and whether the HFEA is capable of effectively assessing cutting-edge technology or carrying out a detailed assessment of the clinical capabilities and compliance of HFEA-regulated clinics.

This session was the first of two events organised by PET and focused on updating the HFE Act. The second event, titled 'Fertility Frontiers: What Is a "Permitted" Embryo in Law?', is scheduled for Wednesday 25 May 2022 and my colleague, Of Counsel Julian Hitchcock, will be speaking. Registration is free and we look forward to another lively debate on a fascinating area of life sciences regulation.

In the UK, fertility treatment and embryo research have a dedicated statutory regulator, the Human Fertilisation and Embryology Authority (HFEA). The UK Government has signalled that the laws which define the HFEA's powers could be revised in the near future.

https://pet.secure.force.com/PETEvents/PETEve

Embryology

Widower in High Court fight over use of embryo created after IVF treatment – Forres Gazette

May 6, 2022 medical

The Royal Courts of Justice on The Strand in London (Andrew Matthews/PA)

A 38-year-old widower wants a High Court judge to allow him to use an embryo created using his sperm and the eggs of his late wife after IVF treatment.

Investment manager Ted Jennings, of Highbury, north London, has asked Mrs Justice Theis to rule that it would be lawful for him to use the embryo, which was created in 2018 and has been stored, in treatment with a surrogate mother.

Lawyers representing the Human Fertilisation and Embryology Authority said Mr Jennings application should be dismissed.

They argued that it would not be lawful to use the embryo because Mr Jennings wife, accountant Fern-Marie Choya, who died in 2019, aged 40 after becoming pregnant, had not provided written consent.

The judge considered Mr Jennings application at a public hearing in the Family Division of the High Court in London on Thursday and is expected to deliver a written ruling in the near future.

Jenni Richards QC, who led Mr Jennings legal team, told the judge that Mr Jennings and Ms Choya, who both moved to Britain from Trinidad, had married in 2009.

She said they had struggled to conceive naturally and underwent three cycles of IVF treatment in 2013 and 2014 without success.

Ms Choya had conceived naturally in 2015 and 2016 but both pregnancies ended in miscarriage.

The couple had undergone further IVF cycles, in 2017 and 2018, and re-mortgaged their home in order to afford private treatment.

Ms Richards said a positive pregnancy had been confirmed in late 2018.

She said Ms Choya had developed complications with her pregnancy at 18 weeks, which resulted in a uterine rupture, and died in February 2019.

Ms Richards said one embryo, the subject of the application, remained in storage.

She said the issue related to a legal requirement that consent be recorded in writing and signed by the person giving it.

the evidence is that Ms Choya would have wanted Mr Jennings to be able to use their partner-created embryo in treatment with a surrogate in the event of her death, said Ms Richards in a written case outline.

In all the circumstances, it can, and should, be inferred that Ms Choya would have provided written consent to Mr Jennings being able to use their partner-created embryo in treatment with a surrogate in the event of her death had she been given the opportunity to do so.

Ms Richards added: Ms Choya had no opportunity, through no fault of her own, to provide that consent in writing.

She said preventing Mr Jennings using the embryo would be a significant interference with his human right to respect for private and family life and prevent him from fulfilling the couples wish to have a child.

Kate Gallafent QC, who led the Human Fertilisation and Embryology Authoritys legal team, argued that without written consent it would not be lawful to use the embryo.

She said the authority was sympathetic and told the judge that its sole interest was to promote compliance with a statutory scheme.

Mr Jennings seeks a declaration from the court that it is lawful to use an embryo created using his gametes and those of his late wife Ms Choya in the treatment of a surrogate, she told the judge in a written case outline.

However, it is common ground between the parties that Ms Choya did not provide written consent to the embryo being used by Mr Jennings in treatment with a surrogate in the event of her death.

She said the authoritys primary submission was that: In the absence of such written consent, it is not lawful to use the embryo in treatment with a surrogate.

Ms Gallafent said the requirement of written consent was an express statutory condition set out in the 1990 Human Fertilisation and Embryology Act and central to the legislative regime.

Mrs Justice Theis said she aimed to deliver a written ruling in the near future.

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Widower in High Court fight over use of embryo created after IVF treatment - Forres Gazette

Embryology

Australia Moves Ahead Cautiously With ‘3-Parent IVF’ – WIRED

May 6, 2022 medical

Australias cautious approach is similar to that of the UK, where Parliament voted to legalize mitochondrial donation in 2015. There, only one clinic, Newcastle Fertility Centre, is licensed to perform the procedure. It must appeal to the UK's fertility agency, the Human Fertilisation and Embryology Authority, to approve patients on a case-by-case basis.

Under the new Australian law, mitochondrial donation will initially be offered at just one fertility clinic as part of a clinical trial. The trial likely wont begin for another year or two, and once underway it is expected to last 10 to 12 years. Families interested in joining the trial will need to attend counseling to discuss potential risks involved in mitochondrial donation, and participants will ultimately need to be approved by a board of experts.

The law requires researchers to track participants' pregnancies and birth outcomes, including any miscarriages, premature births, birth defects, or instances of mitochondrial disease among babies born from these pregnancies. Investigators will also monitor the ongoing health and development of children born as a result of the trial.

In contrast to the law in the UK, Australian children born from this procedure will be able to access identifying information about the egg donor in the same manner as children born as a result of egg donation.

The number of participants for the trial hasnt been determined yet, but according to an April 10 funding announcement by the Australian government, the trial must provide a pathway for impacted families to access the technology. While about one in 5,000 babies are born in Australia with a severely disabling form of mitochondrial disease, not all women with mitochondrial disease will need access to this technology, says Megan Munsie, a stem cell scientist and professor of emerging technology at the University of Melbourne.

The reform rightly limits the use of mitochondrial donation to circumstances where this is the only option available to them to reduce the risk of a womans child inheriting mitochondrial DNA disease that is likely to result in serious illness, she says. Depending on how the disease affects their mitochondria, other assisted reproductive technologies, such as preimplantation genetic testing, will be sufficient. This type of testing allows prospective parents going through IVF to select only healthy embryos to implant.

Even after Australias trial period, its not a given that the technology will be made more widely available to women who carry mitochondrial DNA mutations. It is not yet certain that the technology will be implemented clinically, says Catherine Mills, director of the Monash Bioethics Centre in Australia. That will depend on the outcome of the clinical trial, which will weigh safety and efficacy.

There are two major safety concerns with the procedure, says David Thorburn, a mitochondrial disease researcher at the Murdoch Children's Research Institute in Melbourne. One is that a small amount of carryover mitochondrial DNA from the mother could end up in the baby. There may be potential for this to increase to a higher amount during development, such that it could result in mitochondrial disease, he says.

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Australia Moves Ahead Cautiously With '3-Parent IVF' - WIRED