Category Archives: Cell Biology

Cell Biology

Native American and Indigenous Community Takes Shape At UConn – UConn Today – University of Connecticut

When Kat Milligan-McClellan arrived at UConn in fall 2020, she looked around at the rolling hills, the autumn leaves, and the 18th-century buildings, and immediately knew: Something was missing.

There were as many as four monuments to Nathan Hale in my town, says the assistant professor of molecular and cell biology and member of the Inupiaq people. But there was nothing about Native Americans no markers, no monuments, no acknowledgments. Nothing.

And UConn was no different.

We were struck by the level of Indigenous erasure on campus, says Sandy Grande, professor of political science, director of the new Native American and Indigenous Studies Initiative and a Quechua national. Youre hard-pressed to find anything on campus that speaks to the continued presence of Indigenous peoples.

Yet, what Grande and Milligan-McClellan did find was a committed group of students hard at work building a UConn Native American community: inviting and hosting prominent Native American speakers, creating Native American student organizations and academic communities, and supporting a mentoring program for Indigenous youth.

Student involvement has driven UConns efforts to reclaim an Indigenous presence on campus, says Grande. And together in intergenerational partnership, we now have potential to do so much more.

Native student power

In 2021, only 40 of the more than 32,000 UConn students identified as Native American or Indigenous. Grande and her colleagues know of only six Native American faculty.

It wasnt surprising, then, that in her speech at the 2022 Commencement Ceremonies, student speaker Sage Phillips 22 (CLAS), a member of the Penobscot Nation, said that when she was applying to colleges, it was clear rather quickly that UConn did not meet my list of conditions.

I did not see a strong Native and Indigenous Studies Department, nor a large community of support for Indigenous students, she said in her speech.

It was her father who counseled her to embrace the opportunity to build an Indigenous community at an institution that needed one.

Leading a small but dedicated group of Native American students, Phillips came to UConn in 2018 and founded the UConn Native American and Indigenous Students Association (NAISA), in partnership with UConns Native American Cultural Programs (NACP). Fellow student Zoe Blevins 22 (CLAS), a human rights major, founded the UConn Indigenous Nations Cultural and Educational Exchange mentorship program (UCINCEE), which pairs Indigenous youth with undergraduate students from NAISA or NACP with the goal of fostering relations between Indigenous cultures and UConn.

The students also rejuvenated the UConn chapter of the Society for Advancing Native Americans and Chicanos in Sciences (SACNAS) and hosted prominent Native American speakers on campus.

By late 2019, Native and Indigenous programming had risen to an unprecedented level.

Then in 2020, Grande, Milligan-McClellan and Assistant Professor of Anthropology Nate Acebo came to UConn as part of a planned cluster hire to bring diverse scholars and perspectives to UConn.

The professors formed the Native American and Indigenous Studies Initiative (NAISI), which serves as an academic home for the NAIS minor and associated courses and programming to strengthen the Native American and Indigenous community at UConn and beyond.

Milligan-McClellan immediately recognized the sheer amount of effort and care the student community had devoted to their cause. She and her faculty colleagues cites the students as a reason they chose UConn.

The students were the ones who really got us all together, says Milligan-McClellan. Its amazing to have such a strong student community.

Having dedicated the entirety of my undergraduate career to expanding our resources and community on campus, it felt as though we had done something right when Sandy, Kat, and the rest of the NAISI team came to UConn, Phillips says. They saw our potential and trusted us and our efforts.

With the addition of Assistant Professor of History Hana Maruyama and Assistant Professor of Educational Leadership Chen Chen, UConns first critical mass of scholars focused on the study of Indigeneity and settler colonialism was created.

A history erased

The culture and history of Native tribes in the Northeast is unique, says Grande. Northern peoples like the Mohegan, Pequot, and Nipmuc tribes have deeply overlapping histories. Prior to colonization, some tribes were once the same peoples, and those familial ties persist to this day.

Whats more, a fascination with New England colonial history has contributed to the lack of Indigenous knowledge and culture, Grande says.

New England has a history of Native erasure, says Grande, who grew up in Hartford. Children do not learn Native histories. We need to change that.

In collaboration with Glenn Mitoma, then-Director of Dodd Human Rights Impact, Phillips has worked toward this change through the research project Land Grab Connecticut. Inspired by the national Land Grab U and produced through UConns Greenhouse Studios, the project maps land data tied to Connecticut public universities, including UConn, to show how they are intertwined with colonialism, says Grande.

And thats just one step in the right direction. The NAISI faculty see UConn as uniquely positioned to become a center for Indigenous study and community in the Eastern U.S.

With colleagues at other northeastern universities such as Quinnipiac, Eastern Connecticut State University, Yale, Dartmouth, Columbia, and Brown, the faculty plan to build what theyre calling the Quinnehtukqut River Collective named for the Algonquin word giving rise to Connecticut to raise the visibility and significance of Native peoples and culture in the Northeast.

UConns central location and its history as a land-grant university makes it an ideal hub, Milligan-McClellan says.

One of the tenets of being Inupiaq, and of being Native American, is community, she explains. It was drilled in from a very early age: what you do, you do with and for your community.

IndigaPalooza!

The College of Liberal Arts and Sciences Dean Juli Wade and Associate Dean for Diversity, Equity and Inclusion Kate Capshaw have worked hard to bring Grande and her colleagues to UConn, and have been supportive of NAISI from the start, Grande says.

The College brought in five new Native studies faculty pretty much at once thats just unheard-of, says Milligan-McClellan. I thought, I want to be at the ground floor. I want to be able to shape the direction of this Indigenous community at UConn. Thats what drew me here.

With support from UConns Presidents Commitment to Community initiative, NAISI developed and presented a seminar series with panel discussions and external speakers throughout 2021-2022.

The event, colloquially known to organizers and attendees as IndigiPalooza, was co-sponsored by the Womens, Gender, and Sexuality Studies Program and their director, Associate Professor-in-Residence Sherry Zane, along with Associate Professor of English Bhakti Shringapure and her program, the Radical Books Collective.

The program culminated in a two-day conference in April 2022. which was the biggest Native American gathering in UConns history, says Grande.

More than 100 students, faculty and community members from around New England attended standing-room-only events to learn about teaching, research and advocacy for Native American issues.

IndigiPalooza featured discussions on Indigenous women in STEM, presented by Milligan-McClellan; Indigeneity as represented in multimedia, presented by Acebo; and the history of Black and Indigenous schooling and pedagogy, presented by Grande.

It also featured a workshop on integrating decolonial methods and centering Indigenous histories in teaching, and two film screenings: the Emmy-nominated End of the Line: Women of Standing Rock about the Dakota pipeline access controversy, complete with visiting members of the cast; and Beans, a story about a young Mohawk girl coming of age during the Oka Crisis, an Indigenous uprising in Canada in the 1990s.

The series was promoted and bolstered by NACP, which has long sponsored UConn programs for Indigenous Peoples Week and Native and Indigenous Heritage Month, including an annual Rising Sun Powwow in Gampel Pavilion.

The professors credit the Native American and Indigenous Student Association, the group begun by Phillips, as a major precursor to the symposium.

Native Studies at UConn

This fall, 40 Native American students were admitted to UConn, which doubles their representation on campus.

But, since so few students realize that they can study and earn a minor in Native American and Indigenous Studies, the faculty are developing a general-education class to bring the topic to students in their first years in college.

Several new undergraduate courses began last year: Milligan-McClellan taught about historically excluded and underrepresented scientists, which drew from her years of Native activism and knowledge of Black and Indigenous movements on college campuses. Grande taught a class on Native American theory and politics, and is developing a course on Indigenous Elders, aging and politics.

Outside the classroom, Grande, Milligan-McClellan, Acebo and their peers spend time mentoring Native American undergraduates and educating the broader community. There are so few Native American faculty, Grande says, that their labor is in high demand. She loves working to build Native Studies at UConn, but she looks forward to sharing the job with more Native faculty in future years.

Current NAISA president Samantha Gove 24 (CLAS), a sociology and human rights major, also hopes to see more Indigenous faculty in future years.

As a Mashantucket Pequot high school student, I never saw myself going to UConn, she admits. Ten years from now, I hope to see UConn become a university that our local Indigenous youth would be excited to attend because of their Native and Indigenous institutional support and programming, not in spite of their lack of it.

UConn as a land-grant institution has a responsibility to our community, our families, and our ancestors and that responsibility is uplifting our needs and hearing our voices, adds Phillips.

Unfolding Futures

With momentum continuing to build, the NAISI faculty are building relations between UConn and the five recognized Native tribes in Connecticut: the Mohegan, the Mashantucket Pequot, the Schaghticoke, the Golden Hill Paugussett, and the Eastern Pequot. Theyre made contact with key leaders, including Chief Mutwi Muthash (Many Hearts)Lynn Malerba 08 MPA of the Mohegan tribe, who was recently named the first Native American U.S. Secretary of the Treasury.

The NAISI faculty are working toward more physical campus space and creating a greater presence of Native and Indigenous peoples and communities on campus. The recent hire of Visiting Instructor Chris Newell of the Passamaquoddy tribe, one of the founders of the locally-based Akomawt Educational Initiative, and his expertise on approaches to Native American and Indigenous education will go a long way toward creating this presence, says Grande.

In partnership with NAISA and Native students, theyre also advocating for commemoration of Indigenous peoples on campus. This isnt just a gesture, says Milligan-McClellan its among the best ways to make Native students feel welcomed when they first set foot on campus.

It will take many years to accomplish, but their work is just starting and Milligan-McClellan says it doesnt have an end.

All of it is service, but we just think of it as living our lives, she says. Its all community-building, and thats what we do.

Some institutions want scholars who happen to be Indigenous. And other institutions make room for Indigenous scholars, adds Grande. The way we do work is different, and UConn is beginning to understand that.

Read the original post:
Native American and Indigenous Community Takes Shape At UConn - UConn Today - University of Connecticut

Cell Biology

PostDoctoral Research Assistant in Single Cell Mass Spectrometry job with UNIVERSITY OF SURREY | 310566 – Times Higher Education

Chemistry

Location: GuildfordSalary:34,308 to 42,155 per annumFixed TermPost Type:Full TimeClosing Date: 23.59 hours BST on Sunday 23 October 2022Reference: 067422

The University of Surrey is opening a unique national facility for spatially resolved live single cell omics (SEISMIC). This centre will welcome industry and academic users from across the UK. SEISMIC will use the new cutting-edge Yokogawa SS2000 instrumentation to extract single cells, and even subcellular compartments from cells cultured whilst under microscope observation. Extracted cell contents can then be analysed using mass spectrometry omics at Surrey, and within collaborators. The methodology is also compatible with genome and RNA analysis. The SEISMIC award includes funds for researchers to travel to Surrey to conduct experiments. SEISMIC will enable scientific discoveries in a completely new way in distinct areas including drug discovery, infection, stem cell biology, immunity and ageing.

We are looking for motivated, enthusiastic individuals with excellent interpersonal, academic and technical skills to join our growing team and help us to set up and run SEISMIC. The postholder will help to drive forward the analytical measurement capability to enhance the sensitivity and reproducibility of single cell measurements of proteins, metabolites and lipids. The successful applicants will also work with a variety of users using the research base and will have opportunity to undertake development work too. There are therefore excellent opportunities for publication and career development for team-oriented scientists. You will need at least PhD degree in chemistry, biochemistry or related discipline. Experience in biological mass spectrometry would be preferred.

For enquiries and further information please contact Professor Melanie Baileym.bailey@surrey.ac.uk, Tony Whettona.whetton@surrey.ac.ukor Paul Townsendp.townsend@surrey.ac.uk

or more informationand to apply online, please download the further details and click on the 'apply online' button above.

In return we offer a generous pension, relocation assistance where appropriate, flexible working options including job share and blended home/campus working locations (dependent on work duties), access to world-class leisure facilities on campus, a range of travel schemes and supportive family friendly benefits including an excellent on-site nursery.

Click here to find out more about the benefits we offer to support you.

The University of Surrey is committed to providing an inclusive environment that offers equal opportunities for all. We place great value on diversity and are seeking to increase the diversity within our community. Therefore we particularly encourage applications from under-represented groups, such as people from Black, Asian and minority ethnic groups and people with disabilities.

Follow this link:
PostDoctoral Research Assistant in Single Cell Mass Spectrometry job with UNIVERSITY OF SURREY | 310566 - Times Higher Education

Cell Biology

RAPT Therapeutics Strengthens Leadership Team with Two New Key Hires – BioSpace

SOUTH SAN FRANCISCO, Calif., Sept. 28, 2022 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc.(Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, today announced the appointment of Jennifer Nicholson as Senior Vice President of Regulatory Affairs and Quality Assurance and Adnan Rahman as Vice President of Commercial.

It is a pleasure to welcome both Jennifer and Adnan to the RAPT leadership team at this exciting time of growth for the Company, said Brian Wong, M.D., Ph.D., President and Chief Executive Officer of RAPT Therapeutics. The combination of their regulatory, commercial and marketing expertise is invaluable as we advance our RPT193 program into late stage trials in atopic dermatitis and asthma and continue development of FLX475 program in multiple cancer indications.

Jennifer Nicholson Jennifer brings over 20 years of biotechnology and pharmaceutical industry regulatory expertise, with significant experience across all stages of development in oncology including hematologic malignancies and solid tumors. Most recently, she served as Vice President of Regulatory Affairs at Kronos Bio. Prior to Kronos Bio, she was Head of Global Regulatory Science at Acerta Pharma, a member of the AstraZeneca Group. Jennifer was the Global Regulatory Lead for the Calquence (acalabrutinib) US NDA, which was granted accelerated approval in 2017, as well as for subsequent global filings. Prior to joining Acerta, Jennifer was Senior Director of Regulatory Affairs at Bavarian Nordic, where she focused on immuno-oncology and vaccine products. Earlier in her career, Jennifer worked as the Global Regulatory Lead on various hematology and oncology products at Jazz Pharmaceuticals, Onyx Pharmaceuticals and Genentech. Jennifer holds a B.S. in Biochemistry and Cell Biology from the University of California, San Diego and an M.H.A. from the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill.

Adnan RahmanAdnan brings over 20 years of biopharmaceutical commercial and marketing expertise. Most recently, he served as Global Commercial Lead of Dermatology at Arena Pharmaceuticals, acquired by Pfizer., where he led global commercial strategy for its principal asset, Etrasimod, in atopic dermatitis and alopecia areata. Prior to Arena Pharmaceuticals, he was U.S. Commercial Director of XGEVA (denosumab) at Amgen and held various senior marketing positions in oncology, bone health and inflammation business units. Earlier in his career, Adnan held various marketing positions at Pharmacia and Procter & Gamble. Adnan holds an M.B.A. from Rutgers University and an M.A and B.A. in Electrical Engineering from University of Cambridge.

About RAPT Therapeutics, Inc.RAPT Therapeutics is a clinical stage immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology. Utilizing its proprietary discovery and development engine, the Company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, RPT193 and FLX475, each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of inflammation and cancer, respectively. The Company is also pursuing a range of targets that are in the discovery stage of development.

RAPT Media Contact:Aljanae Reynoldsareynolds@wheelhouselsa.com

RAPT Investor Contact:Sylvia Wheelerswheeler@wheelhouselsa.com

See original here:
RAPT Therapeutics Strengthens Leadership Team with Two New Key Hires - BioSpace

Cell Biology

Research Fellow, Department of Anatomy and Physiology job with UNIVERSITY OF MELBOURNE | 310587 – Times Higher Education

Location:ParkvilleRole type:Full time; Fixed-termfor 12 monthsFaculty: Medicine, Dentistry and Health SciencesDepartment/School:Department of Anatomy and PhysiologySalary:Level A $77,171 $104,717p.a. (pro rata for part-time) plus 17% super

The University of Melbourne would like to acknowledge and pay respect to the Traditional Owners of the lands upon which our campuses are situated, the Wurundjeri and Boon Wurrung Peoples, the Yorta Yorta Nation, the Dja Dja Wurrung People. We acknowledge that the land on which we meet and learn was the place of age-old ceremonies, of celebration, initiation and renewal, and that the local Aboriginal Peoples have had and continue to have a unique role in the life of these lands.

About the Department of Anatomy and Physiology

The Department of Anatomy and Physiology has only recently come into fruition and is an amalgamation between the Departments of Anatomy and Neuroscience and Physiology. Both Departments have long and illustrious history and have come together to produce a Department with a remarkable breadth and depth in research expertise that underpin our key research themes of neuroscience, metabolism and cardiovascular sciences, muscle biology, and cell biology.

The goal of the combined department is to remain at the forefront of scientific research aimed at understanding the structure and function of the human body in health and disease, employing novel and imaginative research methods.

About the Role

The Research Fellow will work within the Wells Laboratory on NHMRC funded research. The role will conduct supervised research using pluripotent stem cells to model macrophage biology. The role will also require the provision of support for research projects and programs within the laboratory, including administration and maintenance and use of information systems.

Responsibilities include:

About You

You will be an experienced research fellow with experience and expertise in pluripotent stem cell culture or human macrophage biology. Your excellent verbal and written communication skills allow you to demonstrate effective research collaboration and engagement. Your strong organisational skills allow you to maintain accurate and detailed laboratory records, and manage competing priorities.

You will also have:

About the University

The University of Melbourne is consistently ranked amongst the leading universities in the world. We are proud of our people, our commitment to research and teaching excellence, and our global engagement.

Benefits of Working with Us

In addition to having the opportunity to grow and be challenged, and to be part of a vibrant campus life, our people enjoy a range of rewarding benefits:

To find out more, visithttps://about.unimelb.edu.au/careers/staff-benefits.

Be Yourself

We value the unique backgrounds, experiences and contributions that each person brings to our community and encourage and celebrate diversity. First Nations people, those identifying as LGBTQIA+, females, people of all ages, with disabilities and culturally and linguistically diverse people are encouraged to apply. Our aim is to create a workforce that reflects the community in which we live.

Join Us!

If you feel this role is right for you, please submit your application including a brief cover letter, your resume and your responses against the selection criteria^ (found in the Position Description) for the role.

^For information to help you with compiling short statements to answer the selection criteria and competencies, please go tohttp://about.unimelb.edu.au/careers/selection-criteria

We are dedicated to ensuring barrier free and inclusive practices to recruit the most talented candidates. If you require any reasonable adjustments with the recruitment process, please contact us athr-talent@unimelb.edu.au.

Please note: To be considered for this role you must havecurrent valid work rights for Australia

osition Description:0057175 - PD.pdf

Applications close:27 Oct2022 11:55 PMAUS Eastern Standard Time

View post:
Research Fellow, Department of Anatomy and Physiology job with UNIVERSITY OF MELBOURNE | 310587 - Times Higher Education

Cell Biology

LBUSD’s Teacher of the Year is a homegrown educator who explains the world with literature Long Beach Post News – Long Beach Post

For Lee Underwood, that moment arrived when he was a high school student at nearby St. John Bosco. One class in particular changed his outlook on the world and inspired the next few decades of his life.

As of last week, that moment has officially come full circle for Underwood, who was recognized as the Long Beach Unified School Districts Teacher of the Year.

An Advanced Placement English Literature and Composition teacher at Millikan High School, Underwood credits his former AP Literature teacher and soccer coach, Jim Cross, for helping spark his love of English and for helping to inspire his career path.

He had this passion for books and teaching poetry that I had just never seen before, recalled Underwood. Me and my angsty self at that time, really connected with the way that he saw poetry as a living thing, as a salve for the troubled soul, or even as a path to self-transformation. So I would read these poets and these books and he would talk about them in ways that really allowed me to make sense of myself.

As the son of a teacher, Underwood spent countless hours in his moms classroom growing up. During his college years as a student at Cal State Long Beach, Underwood again drew inspiration from an English professor, Joe Potts, who helped shape his view on what it means to be a teacher.

He was the one that really got me fired up about pedagogy, Underwood explained. The idea that teachers are artists and their content is their palette; the books they teach, the way that they teach, all those things are very creative processes that the teacher can bring into the classroom. And I really liked that idea. It was at that moment that I decided to go full force into English education in college and pursue my teaching credential.

Underwood started his teaching career at Millikan back in 2006, as a 23-year-old fresh out of his student teaching program. Hes now in his 17th year on campus and has been inspiring his students the same way Mr. Cross did for him.

Underwood said he enjoys cultivating a classroom environment where students can discuss major issues affecting their everyday lives. He acknowledged that those discussions have evolved in the past few years due to the global pandemic and social unrest across the globe. Through literature, hes helped students gain different perspectives on some of the big, complex issues theyre seeing in the world.

The fantastic thing about teaching a humanities class is that its exactly the right place for a student to try to make sense of things that sometimes dont make sense to them, he explained. Ive seen students become much more serious about loss and grief, because its very possible that these students have seen much more of that over the last couple of years than they ever have before. Im in a really unique position to have these students ask these questions of themselves and to guide them through their own thinking using these texts.

One of his former students, Astrid Quirarte, wrote a letter of support for Underwood winning Teacher of the Year while she was attending UC Berkeley to study molecular and cell biology. Her words spoke to Underwoods dedication to his students, and also his willingness to incorporate contemporary issues into his curriculum.

In all my years in school, I have never met a teacher as approachable and caring as Mr. Underwood, Quirarte wrote. Of all Mr. Underwoods attributes, I consider his greatest to be the genuine care he has for all of his students. He would spend extra time after class reading and editing our college application essays, something I greatly benefitted from as a first-generation college student As a Latinx student, I had encountered multiple English classes that incorporated literature that was not representative of the student body and the real-world challenges students faced. Mr. Underwoods integration of contemporary issues regarding discussions of class, race, sex and gender identity was the first time I ever felt seen in the classroom setting.

Underwood described the Teacher of the Year award as an immense honor but alsosomewhat ironicallyhe struggled to put his emotions into words.

It just melts my heart, I dont know how else to explain it, Underwood said. Nothing, no amount of money can take the place of the words that Astrid wrote about me. It makes me realize that this is the right place to be.

Im exactly in the right place.

Local history: No soapProcter & Gambles Long Beach plant closed in 1988

Read this article:
LBUSD's Teacher of the Year is a homegrown educator who explains the world with literature Long Beach Post News - Long Beach Post

Cell Biology

University subject profile: biology – The Guardian

What youll learnThe biosciences are a wide field including human biology, bioinformatics, botany, zoology, genetics, microbiology and biochemistry. What youll learn depends on how you decide to specialise you could learn the fundamentals of cell biology, the computer skills needed to understand protein sequences, or the mating habits of orangutans.

Youll know how to research information, apply it and use specialist equipment. And youll develop an understanding of the ethical considerations associated with your field of study.

How youll learnYoull spend a lot of your time in the laboratory doing practical work, and most courses require students to conduct their own research. There will probably be group projects, so youll learn how to work in a team. Chances are youll be taught by those at the cutting edge of research. Assessment will involve a mix of coursework, projects and exams. Some courses offer a year in industry a good way of building your CV.

Entry requirementsUniversities are likely to expect biology at A-level or equivalent, and sometimes chemistry. They may also ask for an additional science or maths (or further maths or pure maths). Course requirements will likely range from CCC to AAA. You may be required to attend an interview and give a short presentation on a topic in your field of study.

What job can you get?Lots of jobs are suited to biology graduates, but if you want to work as a scientist youll need to do further study at postgraduate level. If you want to specialise, your degree should give you the skills to turn your hand to forensic science, immunology and toxicology, to name but a few. You could then find suitable research posts in the public and private sector particularly in industry or in academia. Many biology graduates end up in the health and social care sector, and in education.

The skills you acquire will also qualify you for jobs outside the lab. Work can be found in local and central government, in NGOs, doing conservation work, and in teaching.

Continued here:
University subject profile: biology - The Guardian

Cell Biology

Childhood leukemia treatment 2022: Where we are now and what it takes – EurekAlert

image:Prof. Christina Peters, MD, points out: "We have published highly topical and clinically relevant manuscripts that are of utmost importance for the treatment of children with high-risk acute lymphoblastic leukemia. One of the most burning questions for me is whether we still need stem cell transplantation in the era of modern immunotherapies." view more

Credit: St. Anna Children's Cancer Research Institute

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, generally curable with contemporary chemotherapy. However, if the disease is classified as high-risk ALL and a stem cell transplantation becomes inevitable, total body irradiation is still the treatment of choice prior to transplantation. This was the conclusion drawn from the FORUM study, including 35 countries on five continents (Peters et al., Journal of Clinical Oncology 2020).

"As the largest study on this topic to date, we published the results in the top-ranked Journal of Clinical Oncology. Soon after that, Frontiers invited us the international transplant consortium for ALL to publish a collection of reviews and scientific reports on ALL in children," recalls Christina Peters, Affiliated Clinician at St. Anna Children's Cancer Research Institute (St. Anna CCRI) and Senior Physician at St. Anna Children's Hospital. The editorial board of this Research Topic is formed by Christina Peters together with Assoc.-Prof. Adriana Balduzzi, MD (University of Milano Bicocca, Italy) and Prof. Peter Bader, MD (Goethe University Frankfurt am Main, Germany).

Life at the price of long-term side effects?Although total body irradiation and hematopoietic stem cell transplantation (HSCT) from healthy donors can be life-saving, long-term side effects sometimes have a massive impact on the quality of life of children and young adults. These include organ damage, growth retardation, and the development of secondary cancers. Hence, there was a dire need to clearly outline recent and previously published data, as well as to discuss potential new approaches, as did the aforementioned reviews.

"One of the most burning questions for me is whether we still need stem cell transplantation in the era of modern immunotherapies," Christina Peters points out. In the future, CAR-T cell or antibody therapies directly targeting leukemia cells could replace HSCT, which is addressed by three of the reviews mentioned. Jochen Bchner, MD, PhD, and colleagues are discussing the question of whether and when CAR-T cell therapy could be considered to bridge the time until transplantation and under what conditions it could replace transplantation. Another review, authored by Assoc.-Prof. Tony H. Truong, MD, and colleagues, is dedicated to the question which children should receive a stem cell transplantation at all. Of course, transplantation should only be considered for those patients who would not have a realistic chance of survival with 'milder' therapies. But it is exactly these boundaries that are currently shifting.

More than 59,000 views of our workSo far, the review of Bianca A. W. Hoeben, MD, PhD, and colleagues, which deals with new methods of total body irradiation, has had the most views in this online collection. "In total, we have more than 59,000 views of our Research Topic by now. Accordingly, it seems to be on many people's minds whether and how we can improve transplantation methods to reduce side effects," says Christina Peters. For example, different radiotherapy centers have developed new methods of total body irradiation to achieve a lower irradiation dose in certain organs. There are, however, limitations to shield organs at risk without compromising the anti-leukemic and immunosuppressive effects the latter to preserve a rejection of the transplanted cells.

In addition to the aforementioned long-term effects of irradiation and transplantation, acute side effects of transplantation also play a major role. These include infections during the period in which the immune system reconstitutes (Olga Zajac-Spychala et al.), or complications arising from a donor cells attack against the patient's healthy tissue. The prevention and treatment of the so-called Graft-versus-Host Disease are addressed by six of the articles in this Research Topic (Steven J. Keogh et al., Anita Lawitschka et al., Jacob Rozmus et al., Agnieszka Sobkowiak-Sobierajska et al., Matthias Wlfl et al., Natalia Zubarovskaya et al.).

"The publication of this Research Topic is a huge success for St. Anna CCRI. Together with the valuable contributions of a number of clinicians of St. Anna Children's Hospital, we have published highly topical and clinically relevant manuscripts that are of utmost importance for the treatment of children with high-risk ALL," highlights Christina Peters.

- - -

About the FORUM StudyThe FORUM study demonstrated that patients over four years of age with high-risk ALL in need of a stem cell transplantation live longer and have a lower risk of relapse when they receive total body irradiation instead of chemotherapy in preparation for transplantation. After random assignment of 417 pediatric patients with high-risk ALL, a futility stopping rule was applied because it became apparent that patients receiving chemo-conditioning had a lower chance of cure and survival. FORUM is a randomized, international, multicenter phase III trial designed to investigate whether chemotherapy with fludarabine, thiotepa, and busulfan or treosulfan is non-inferior to total body irradiation plus etoposide as preparation prior to transplantation. The study, led by Christina Peters, is the result of a collaboration among international study groups (AIEOP-BFM-ALL-SG, IBFM-SG, INTREALL-SG, and EBMT-PD-WP).

Frontiers Research TopicThe Frontiers in Pediatrics "Research Topic" Allogeneic Hematopoietic Stem Cell Transplantation for Children with Acute Lymphoblastic Leukemia in the Era of Immunotherapy is available for download here: https://www.frontiersin.org/research-topics/19704/allogeneic-hematopoetic-stem-cell-transplantation-for-children-with-acute-lymphoblastic-leukemia-in#overviewThe specific thematic areas envisaged to be addressed in this article collection are the following:

Are HLA-identical siblings still the best available donor for ALL? The challenge of treating older children: what is the best transplant strategy for Adolescents and Young Adults (AYAs)? Tyrosine Kinase Inhibitors (TKIs) for Philadelphia Chromosome positive (Ph+) and Ph-like ALL: could we omit Hematopoietic Stem Cell Transplantation (HSCT)? Bispecific Antibodies before HSCT: less toxicity for better transplant outcome? CAR-T cell therapy: only bridge to transplant? T-cell depletion: Cyclophosphamide after transplantation versus in vitro T-cell depletion Why is Total Body Irradiation so effective in high-risk ALL? Total Body Irradiation forever? New chemotherapeutic options for irradiation-free conditioning Minimal Residual Disease (MRD): Which level of negativity is relevant? Current treatment options for acute Graft-versus-Host-Disease (GVHD) in children Current treatment options for chronic GVHD in children Immunoreconstitution and chimerism: a different story compared to adults? Non-relapse mortality after HSCT: where are we now? High-risk ALL: Transplant indications in 2021 COVID-Infection after allogeneic stem cell transplantation Transplantation for the youngest: better than chemotherapy?

About Christina PetersChristina Peters, MD, is Professor of Pediatrics at the Department of Stem Cell Transplantation of St. Anna Children's Hospital and Affiliated Clinician at St. Anna Childrens Cancer Research Institute in Vienna. She is principal investigator of active studies within the European Society for Blood and Marrow Transplantation (EBMT) and the International Berlin Frankfurt Mnster Study Group (IBFM) for the treatment of pediatric leukemia. Her research interests include allogeneic hematopoietic transplantation in children and adolescents with malignant and non-malignant diseases from related and unrelated donors, infectious and toxic complications after stem cell transplantation, adoptive therapies for hematological malignancies and family oriented rehabilitation for children with life threatening diseases.

Christina Peters chaired the EBMT Pediatric Diseases Working Party between 2008 and 2014. She has authored and co-authored numerous papers in peer-review journals such as The Lancet, The New England Journal of Medicine, or The Journal of Clinical Oncology. Christina Peters acts as a regular reviewer of publications for hematology, pediatric and leukemia journals. She is a member of many professional societies including IBFM, the Center for International Blood and Marrow Transplant Research (CIBMTR), the German and Austrian Society of Pediatric Hematology and the Austrian Gene Therapy Commission. Furthermore, Christina Peters is a member of the Advisory Board of the Austrian Ministry of Health, the Bioethical committee of the Austrian Prime Minister and member of the European Network Pediatric Research at the European Medicines Agency EMA (ENPREMA).

About St. Anna Childrens Cancer Research Institute, St. Anna CCRISt. Anna CCRI is an internationally renowned multidisciplinary research institution with the aim to develop and optimize diagnostic, prognostic, and therapeutic strategies for the treatment of children and adolescents with cancer. To achieve this goal, it combines basic research with translational and clinical research and focus on the specific characteristics of childhood tumor diseases in order to provide young patients with the best possible and most innovative therapies. Dedicated research groups in the fields of tumor genomics and epigenomics, immunology, molecular biology, cell biology, bioinformatics and clinical research are working together to harmonize scientific findings with the clinical needs of physicians to ultimately improve the wellbeing of our patients.www.ccri.at http://www.kinderkrebsforschung.at

About St. Anna Children's HospitalEstablished in 1837 in the former suburb of Schottenfeld, St. Anna was the first children's hospital in Austria and the third independent hospital in Europe dedicated exclusively to the health of children. St. Anna Children's Hospital has evolved into an institution that provides state-of-the-art medical care. Thus, in addition to its performance as a general children's hospital, the Center for Pediatrics and Adolescent Medicine has also been able to establish an excellent reputation throughout Austria and internationally over the past 40 years as a center for the treatment of pediatric hematologic disorders and tumor diseases (cancer).www.stanna.at

Frontiers in Pediatrics

People

Allogeneic Hematopoetic Stem Cell Transplantation for Children with Acute Lymphoblastic Leukemia in the Era of Immunotherapy

The authors declare that the editorial of this Research Topic was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Originally posted here:
Childhood leukemia treatment 2022: Where we are now and what it takes - EurekAlert

Cell Biology

Photys Therapeutics Debuts with $75 Million Series A Funding to Advance New Class of Bifunctional Molecules for Precision Phosphorylation to Modulate…

News and research before you hear about it on CNBC and others. Claim your 1-week free trial to StreetInsider Premium here.

- Phosphorylation-inducing chimeric small molecules (PHICS) are a new class of bifunctional medicines that direct and repair aberrant and dysfunctional proteins

- PHICS enable precise phosphorylation, an important post-translational modification that controls protein function, including activation, stabilization, trafficking, inactivation, and degradation

- Led by a strong foundational management team of respected industry veterans with deep experience in successful drug discovery and corporate development

BOSTON--(BUSINESS WIRE)--Photys Therapeutics, the pioneer in the development of phosphorylation-inducing chimeric small molecule medicines (PHICS), founded by Longwood Fund and Dr. Amit Choudhary of Brigham and Womens Hospital and the Broad Institute of MIT and Harvard, today announced a $75 million Series A financing led by MPM Capital and joined by Omega Funds, Longwood, 8VC, Arkin Bio, Mass General Brigham Ventures, MRL Ventures Fund, the therapeutics-focused corporate venture fund of Merck & Co., Eli Lilly and Company, and Heritage Medical Systems. Through induced proximity, PHICS enhance the pairing of specific kinases, the enzymes responsible for protein phosphorylation, with disease target proteins, unlocking a new approach to treatment of underserved diseases.

Many current chimeric and bifunctional modalities focus on protein degradation, which limits their range of addressable diseases, said Edward Holson, PhD, co-founder and Chief Scientific Officer, Photys. Photys expands this functionality, using PHICS to recruit kinases and induce phosphorylation, a key post-translational modification that controls many protein functions, including activation, stabilization, localization, trafficking, degradation, and inactivation.

The foundational biology of kinases is well-understood, and decades of screening has yielded potent kinase binders, said Brian Fenton, Chief Executive Officer. Our approach builds on this foundation and leverages the diversity of kinase function towards treating cancer and other critical immune, metabolic, and rare diseases.

Dr. Choudharys transformational research has provided Photys with a roadmap to expand the native function of kinases to treat disease, said David Steinberg, Chairman and Founding CEO of Photys, and General Partner at Longwood Fund. We look forward to building on his unique insights to establish a broad pipeline of therapeutics that can potentially enhance and extend the lives of patients.

Dr. Lizzie Ngo, Longwood Fund Principal, acted as a co-founder alongside Dr. Choudhary, Mr. Steinberg, and Dr. Holson. Dr. Ngo and Mr. Steinberg also joined the Board of Directors along Luke Evnin, PhD, co-founder and Managing Director of MPM Capital; Alon Lazarus, PhD, Investment Manager, Arkin Bio; Briggs Morrison, MD, President, Head of R&D, and board member at Syndax Pharmaceuticals and Executive Partner at MPM Capital; and Otello Stampacchia, PhD, founder of Omega Funds.

Dr. Holson is a co-founder and Chief Scientific Officer (CSO) of Photys. Dr. Holson has worked in drug discovery for over 20 years as a scientist, founding director, CSO and scientific advisor across multiple organizations, including Amathus Therapeutics, Atlas Venture, KDAc Therapeutics, the Broad Institute of MIT and Harvard, and Merck & Co.

Brian Fenton was named President and CEO of Photys in September of this year and brings over three decades of biopharma leadership experience. He previously served as Chief Business Officer at Translate Bio and spent several years working in the Rare Disease Business Development Group at Shire Pharmaceuticals. He has successfully identified, led, and executed multiple strategic transactions during his career in corporate development. Mr. Fenton earned his BA in Biochemistry from University of Massachusetts, Amherst, MS in Chemical Engineering from University of Virginia, and MBA at Worcester Polytechnic Institute. The Photys Scientific Advisory Board consists of scientific founder Dr. Amit Choudhary; Eric Fischer, PhD, Independent Investigator at Dana-Farber Cancer Institute; Tony Hunter, PhD, Professor and Renato Dulbecco Chair in Cancer Research at the Salk Institute; Angela Koehler, PhD, Associate Professor of Biological Engineering, Koch Institute, Institute Fellow at the Broad Institute of MIT and Harvard and Co-Director of the Swanson Biotechnology Center High-Throughput Screening Facility; Dan Nomura, PhD, Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology at the University of California, Berkeley and Adjunct Professor in the Department of Pharmaceutical Chemistry at UCSF; and Wendy Young, PhD, Executive Partner at MPM Capital.

About Photys Therapeutics

Photys Therapeutics, founded by Longwood Fund and Dr. Amit Choudhary of Brigham and Womens Hospital and the Broad Institute of MIT and Harvard, is advancing Phosphorylation Inducing Chimeric Small Molecules (PHICS), a proprietary new class of bifunctional medicines that direct and repair protein phosphorylation to treat a range of diseases including cancer, immune, metabolic, and rare diseases.

Post-translational modifications, particularly phosphorylation, are ubiquitous throughout the human proteome and play a central role in cellular function. Through induced proximity, PHICS enhance the pairing of specific kinases, the enzymes responsible for protein phosphorylation, with disease target proteins. PHICS can induce precise phosphorylation at native and/or non-native sites, modulating key functions including activation, stabilization, trafficking, localization, phospho-antigen presentation, inactivation, degradation and interactions of proteins. Harnessing well-established biology and chemistry in kinases and bifunctionals in new ways, the PHICS approach unlocks diverse classes of targets.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220908005074/en/

Media:Mariesa Kemble[emailprotected]

Source: Photys Therapeutics

Read more from the original source:
Photys Therapeutics Debuts with $75 Million Series A Funding to Advance New Class of Bifunctional Molecules for Precision Phosphorylation to Modulate...

Cell Biology

New in-silico-designed protein ‘probes’ could pave the way to early diagnosis of neurodegenerative diseases – EurekAlert

image:Zoom-in on single cultured mammalian cells in which TDP-43 has been induced to aggregate. In this system, the cells produce TDP-43 fused to a green fluoresce molecule, to be able to detect whether the protein forms insoluble granules (green fluorescent dots). The RNA probe is labelled with a red fluorescent tag. The yellow colour, given by the overlap between the green of TDP-43 and the red of the RNA probe, signifies that the probe can search and find its protein target in live cells, suggesting that it could be use as a detection tool to track the progress of TDP-43 aggregation in disease.Blue: nuclei; green: TDP-43; red: RNA probe; yellow: TDP-43+RNA probe. view more

Credit: IIT-Istituto Italiano di Tecnologia

Genoa (Italy) - 8 September 2022 - A team of researchers from the IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) has designed in silico molecular probes able to track the progress of a protein that misbehaves in different neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD). The probes can be used to study the behavior of the target protein in cell and were tested in collaboration with Sapienza University of Rome, Centre for Genomic Regulation n Barcellona, University of Edinburgh and Kings College London. The research study has been published in Nature Communications.

Created by the RNA Systems Biology group at IIT in Genoa, the probes consist of computer-designed RNA molecules that bind to a neurodegeneration-associated protein named TDP-43. This protein is present in numerous cases of Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD), where it aggregate creating insoluble protein blobs in neural cells, altering their metabolism and function.

The research team was inspired by the protein's natural interactions with RNA molecules to design molecular probes, which are called aptamers, literally molecules made to fit one single target. Their main goal was to obtain a novel approach for tracking the aggregation of neurodegeneration-associated proteins at the very first steps of the process.

"Using our own algorithms, we designed RNA aptamers specific for TDP-43 and used themtogether with advanced microscopy techniques to follow the protein transition towards its aggregated forms explains Gian Gaetano Tartaglia, principal investigator of the RNA System Biology Lab. We can identify TDP-43 aggregates as small as 10 nanometers which, to our knowledge, is the best resolution achieved so far when visualising protein aggregates".

These aptamers could be used to study, at the molecular level, the phenomenon of abnormal protein aggregation typical of several neurodegenerative diseases and would, therefore, pave the way for the development of early diagnosis tools for these disorders.

"We showed that the RNA aptamers can also be used to track TDP-43 in live cells and in real time, detecting all forms of the protein, from the physiological soluble one to the insoluble state, passing by aggregates of intermediate sizes undetectable by standard approaches," adds Elsa Zacco, lead researcher on the project.

The study was carried out by IIT researchers Elsa Zacco, Alexandros Armaos and Gian Gaetano Tartaglia (also at Sapienza University of Rome), with the participation of the groups led by Mathew Horrocks at University of Edinburgh and Annalisa Pastore at Kings College London.

Nature Communications

Experimental study

Cells

Probing TDP-43 condensation using an in silico designed aptamer

23-Jun-2022

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.

Read the original post:
New in-silico-designed protein 'probes' could pave the way to early diagnosis of neurodegenerative diseases - EurekAlert

Cell Biology

More Effective Cancer Immunotherapy: Stanfords New Method To Find Antigens That Trigger Specific Immune Cells – SciTechDaily

Scientists have developed a new method to faster and more accurately predict which antigens will lead to a strong immune response. This could help researchers develop more effective cancer immunotherapies.

A cells secrets can be revealed by its surface. It is decorated with tens to hundreds of thousands of molecules that help immune cells determine friend from foe. Some of those protruding molecules are antigens that trigger the immune system to attack. However, it can be difficult for scientists to identify those antigens, which often vary across individuals, in the molecular forest.

A team of Stanford scientists has developed a new method to faster and more accurately predict which antigens will lead to a strong immune response. Their approach could help researchers develop more effective cancer immunotherapies. The study was led by Polly Fordyce, an Institute Scholar at Sarafan ChEM-H, and will be reported today (September 5, 2022) in the journal Nature Methods.

T cells, a class of immune cells, crawl along and squish past other cells as they patrol the body. They use T cell receptors to molecularly read peptides, or short pieces of proteins which are cradled within larger proteins called major histocompatibility complexes (pMHCs) that project from cell surfaces. Healthy host cells display an array of pMHCs that do not trigger an immune response. However, once T cells recognize disease-indicating peptides, they become activated to find and kill cells bearing these foreign signatures. Understanding how T cells sensitively differentiate these antigenic peptides from host peptides to avoid mistakenly killing host cells has long been a mystery.

A T cell can detect a single antigenic peptide amongst a sea of 10,000 or 100,000 non-antigenic peptides being displayed on cell surfaces, said Fordyce, assistant professor of bioengineering and of genetics.

The key to selectivity is in the T cell crawl. T cells sliding puts stress on the bonds between receptors and peptides, and most of the time, that extra stress is enough to break that bond. But sometimes, it has the opposite effect. Chris Garcia, co-author of the study and professor of molecular and cellular physiology and of structural biology, and others had previously shown that the most antigenic peptides are those whose interactions with T cell receptors grow stronger in response to sliding.

Its kind of like a Chinese finger trap, said Fordyce. When you pull a bit at the receptor-antigen interaction, the binding actually lasts longer.

Identifying the best antigen-receptor pairs requires simultaneously applying that sliding, or shear, force between a peptide and a T cell and measuring T cell activation. Ideally, this would be done thousands of times to get repeatable data for many possible peptide/T cell receptor pairs. However, existing methods are time-intensive and can result in measuring only one peptide with hundreds of T cells in a day.

Postdoctoral scholar Yinnian Feng, the studys first author, developed a trick that allows the team to measure 20 unique peptides interacting with thousands of T cells in less than five hours.

To make a simplified system that mimics cells with dangling peptides, they constructed small spherical beads from a material that expands upon heating and attached a few molecules of a given peptide-studded pMHC to their surfaces. After depositing a T cell atop each bead and waiting long enough for receptors to bind to the peptides, they then very slightly heated the bead. The beads expansion increases the distance between tether points, and the corresponding stretching of the T cell mimics the force it would experience sliding along cells in the body. After exerting that force, the team then measured how active the T cells were.

They could do hundreds of individual experiments in parallel by using beads that are each labeled with a unique color, making it possible to track multiple different pMHCs. They took two sets of pictures tiling across each slide after each run: one set that tells them which pMHC a given bead is displaying and another that tells them how active each T cell atop that bead is. Cross-referencing those images tells them which antigens led to the strongest T cell responses.

In this demonstration of their platform, the research team showed, with 21 unique peptides, that their results confirmed known activating and non-activating peptides for one T cell receptor and uncovered a previously unknown antigen that induced a strong T cell response. Working with the Garcia lab, they have also already begun to address a challenge in immunotherapy: the T cell receptors that form the highest affinity interactions with antigens in the lab are often also activated by non-antigenic peptides in the body. This is a dangerous side effect that leads to the killing of healthy cells.

Using their technology, the team of researchers characterized T cell receptors engineered to specifically recognize tumor antigens without off-target reactivity. In future work, they plan to build libraries of over 1,000 peptides to uncover novel antigens.

The scientists hope that this approach, which is quick and requires few cells, or an optimized form of it could one day be used to improve personalized immunotherapies.

This platform can help improve efforts to engineer T cells that specifically target cancer cells, as well as determine which antigens are capable of potently activating a patients own T cells to more effectively target cancer cells, said Fordyce.

Reference: Bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation 5 September 2022, Nature Methods.DOI: 10.1038/s41592-022-01592-2

Fordyce is a member of Stanford Bio-X, SPARK, and the Wu Tsai Neurosciences Institute, and is a Chan Zuckerberg Biohub investigator. Garcia is a member of Stanford Bio-X, the Stanford Cancer Institute, the Wu Tsai Neurosciences Institute, and a Howard Hughes Medical Institute investigator.

Xiang Zhao and Adam K. White are also authors of the paper.

The work was funded by a Stanford Bio-X Interdisciplinary Initiatives seed grant and the National Institutes of Health.

Go here to see the original:
More Effective Cancer Immunotherapy: Stanfords New Method To Find Antigens That Trigger Specific Immune Cells - SciTechDaily