2024 Marble Center Distinguished Seminar Series

Molecular Bottlebrush Prodrugs and Antibody Bottlebrush Conjugates (ABCs)

Jeremiah Johnson, PhD

Monday April 29th, 2024 (4-5pm EST)

KOCH INSTITUTE LURIA AUDITORIUM

Registration details will be shared soon

The development of targeted cancer therapies that are both effective and safe remains a significant challenge. Tumor-selective nanoparticle-mediated drug delivery strategies, which encompass a broad range of conceptual paradigms, promise to improve patient outcomes; however, many challenges remain to fully realize the potential of such constructs in the clinic. Learnings from decades of research have shown that nanoparticle chemistry, which encompasses composition, size, shape, drug release mechanism, etc., plays key roles in both the biological functions of such systems as well as their translatability. Drawing from these learnings and inspired by antibody–drug conjugates (ADCs), which are amongst the most successful “nanoparticle” delivery constructs in the clinic today, we have invented a molecular bottlebrush prodrug platform that seeks to unlock a broad range of new therapeutic strategies for cancer. This talk will describe the conception of our bottlebrush polymer prodrugs and describe recent examples where this platform has been leveraged to address unanswered questions in cancer therapy, including how synergistic combination therapies discovered in vitro can be translated in vivo, as well as how the timing of immune stimulation can provide access to safe yet more-effective cancer immunotherapies. Finally, monoclonal antibody–bottlebrush conjugates (ABCs) that may overcome some of the limitations of ADCs will be introduced.

About Dr. Jeremiah Johnson: Jeremiah conducted undergraduate research with Prof. Karen L. Wooley at Washington University in St. Louis where he received a B.S. in biomedical engineering with a second major in chemistry. He then received a PhD in chemistry from Columbia University under the mentorship of Prof. Nicholas J. Turro and Prof. Jeffrey T. Koberstein. In 2011, following a Beckman Postdoctoral Fellowship at California Institute of Technology under the guidance of Professors David A. Tirrell and Robert H. Grubbs, he moved to MIT where he is now the A. Thomas Geurtin Professor of Chemistry. He is also a member of the MIT Program for Polymers and Soft Matter (PPSM), the Koch Institute for Integrative Cancer Research, and the Broad Institute of MIT & Harvard. He is Co-Founder of Window Therapeutics Inc. and Electrolyte Solutions Inc., both of which are based on technologies (co)developed in his laboratory at MIT.

Jeremiah received a 2019 ACS Cope Scholar Award, the 2018 Macromolecules-Biomacromolecules Young Investigator Award, the 2018 Nobel Laureate Signature Award for Graduate Education, a Sloan Research Fellowship, the Air Force Young Investigator Award, the Thieme Journal Award for Young Faculty, the DuPont Young Professor Award, the 3M Non-tenured Faculty Award, and an NSF CAREER award. In 2019 and 2023 he was named as a Finalist for the Blavatnik Award for Young Scientists. In 2020 and 2023, nanoparticle constructs from his laboratory were awarded the Assay Cascade Award from the Nanoparticle Characterization Laboratory of the National Cancer Institute. In recognition of his teaching, he was awarded the 2018 MIT School of Science Undergraduate Teaching Prize. The Johnson research group is focused on the invention of methods and strategies for the synthesis of functional (macro)molecules and materials to address fundamental scientific questions and contribute solutions to global challenges including renewable energy storage, chemical sustainability, and human health.

MIT James R. Killian, Jr. Award and Lecture Series

Programming Medical Treatment One Nanolayer at a Time

Tuesday, April 9, 2024 (4pm)

Huntington Hall 10-250, open to the MIT community

Paula T. Hammond, a leading innovator in nanotechnology, has been named the recipient of the 2023-2024 James R. Killian Jr. Faculty Achievement Award. She is Institute Professor at MIT and a member of MIT's Koch Institute for Integrative Cancer Research. She is the Vice Provost for Faculty at MIT as of January 2024.

Professor Hammond, an MIT Institute Professor, was honored for her work designing novel polymers and nanomaterials, which have extensive applications in fields including medicine and energy. More at MIT News.

Killian Lectures are open to the MIT community; no tickets are required, but we do suggest arriving a few minutes early to ensure a seat. Live Streamtext captioning will be available via mobile devices. This lecture will not be webcast, but it will be recorded and posted here in the days following.

The MIT Center for Microbiome Informatics and Therapeutics and the MIT Microbiome Club are proud to invite you to participate in our annual MIT Microbiome Symposium to be held on Friday, March 22, 2024 from 9:30am-5 pm EST at MIT Building E14 located at 75 Amherst St.

The symposium will feature talks from established and young investigators, poster sessions, industry representatives, and a networking social to close the symposium. For more details, please check out the Microbiome Symposium website. This year we are proud to host Dr. Emrah Altindis (Boston College) and Dr. Sophie McCoy (UNC Chapel Hill).

In addition, early-career scientists will present posters and flash talks throughout the day. Please join us in the evening for a networking session with all our speakers and attendees .

Scientists and engineers across many fields and disciplines are united by their work at the nanoscale. Their diverse efforts have helped produce everything from faster microchips to powerful mRNA vaccines. The transformative impact of this work has been spurred by the coordination and focus on U.S. nanotechnology established by the 21st Century Nanotechnology Research and Development Act in 2003. Celebrating such a broad impact and envisioning the future can be quite challenging, but this event will bring together voices from across the emerging technology landscape. There will be experts who can speak on the importance of nanotechnology in quantum engineering, optics, EHS, plastics, DEIA, microelectronics, medicine, education, manufacturing, and more. We can’t predict what will emerge from this lively discussion between researchers, policymakers, members of industry, educators, and the public, but the conversation can only benefit from including more diverse perspectives - especially yours.

The website will be updated as more speakers confirm. Directions to the National Academies can be found here.

AGENDA

9:00-9:05   Welcome and Introduction

9:05-9:30   Opening Remarks on the NNI

9:30-10:15  Morning Keynote

10:15-10:30  Coffee Break

10:30-11:15  Panel: Responsible Development

11:15-12:00  Panel: Fundamental Research

12:00-1:00  Lunch and Networking

1:00-1:45  Keynote Panel: The Future of Nanotechnology

1:45-2:30  Panel: Workforce Development

2:30-2:45  Break

2:45-3:30  Panel: Infrastructure

3:30-4:15  Panel: Commercialization

4:15-5:00  Closing Keynote

Reception to follow

Metrology of Nanoscale Medical and Pharmaceutical Products

This webinar will address measurement challenges in medicine and pharmaceuticals, especially regarding lipid nanoparticles for drug delivery (for example, characterization of surface chemistry and encapsulation). More information will be shared soon.

Pioneering Novel Drug Delivery Systems: The Dr. Paul Janssen Award Symposium 

Since 2004, the Dr. Paul Janssen Award for Biomedical Research has honored scientists who have made a transformational contribution toward the improvement of human health. This prestigious award honors the legacy of Dr. Paul Janssen, an exceptionally gifted and passionate scientist who revolutionized modern medicine and inspired a new generation of researchers.

This half-day virtual symposium will celebrate the 2023 Honoree, Dr. Robert Langer, and his pioneering work.

Carbohydrate coupling for macrophage-targeted RNA therapeutics

Stefan Engelhardt MD PhD

Director, Institute of Pharmacology and Toxicology

Technische Universitaet Muenchen (TUM)

Professor Engelhardt conducts research in the field of signal transduction in the cardiovascular system. He studied medicine at the universities of Regensburg, Munich and Harvard. After his master's degree at the Max Planck Institute of Biochemistry and his PhD and postdoc at the University of Würzburg, Professor Engelhardt headed a junior research group at the DFG Center for Experimental Biomedicine (Rudolf Virchow Center). He was a professor of pharmacology at the University of Würzburg, before being appointed to the Chair of Pharmacology and Toxicology at the TUM in 2008. He also serves as speaker of the German Center for Cardiovascular Research (DZHK) in Munich.

Engineering Microrobots for Medicine: From tissue probing to biosensing to enhanced drug delivery

Monday, December 11, 2023

12:00 p.m. – 1:00 p.m. Luria Auditorium, 76-156

Simone Schürle–Finke’s Responsive Biomedical Systems Lab develops diagnostic and therapeutic systems at the nano-and microscale with to tackle a range of challenging problems in health care, including the increasing cancer burden and infectious diseases. The research focus is twofold: The group develops tools to study disease mechanisms in vitro at the cellular level. We then use this knowledge to inform the design and fabrication of responsive nanosystems that help diagnose or treat diseases with minimal invasion. As such, these systems react for example to locally present signals of the disease environment, such as characteristic pH levels or enzymatic activity. For an additional level of control, simple on-board circuits are added to activate these systems through externally applied stimuli including heat, acoustic, mechanic or electromagnetic signals, resulting in a diagnostic or therapeutic output such as local, on demand release of drugs.

Wyss event: Need for Improved Diagnostic Biomarkers for the Identification and Treatment of Asthma, Sinus Disease, and Respiratory Inflammation

Hosted by Wyss Core Faculty David R. Walt, PhD, Diagnostics Grand Rounds brings clinicians with unmet needs to the Wyss Institute. The goal of these sessions is to inform technology developers about important clinical problems that can help them direct their technology development efforts. Presenters are asked to identify diagnostic needs that will have an impact on the quality of care they deliver.

Many forms of respiratory inflammation, including moderate-to-severe asthma, chronic rhinosinusitis with nasal polyps with or without aspirin/NSAID hypersensitivity, and allergic rhinitis, are classically referred to as diseases of “Type 2 inflammation” or “allergic inflammation”. While true, these overly simplistic descriptions are misleading in their implication that all of the underlying inflammation fits neatly into one type or one box. Unfortunately, the existing diagnostic biomarkers to identify these populations are limited to a few clinical symptoms and the very narrowly focused clinical tests of total serum IgE and peripheral eosinophil count. There are now also 5-7 targeted FDA-approved biologic therapies to treat these respiratory diseases, but the existing diagnostic biomarkers are insufficient to fully immunologically define incoming patients. Therefore, clinicians are left unable to appropriately match each patient with the most appropriate biologic – rather, they are stuck guessing at which treatment might be best for their patient. Dr. Tanya M. Laidlaw, MD, will present and discuss how this unmet clinical diagnostic need may be best approached and solved through development of improved biomarkers.

The 2023 Mildred S. Dresselhaus Lecture recognizes a significant figure in science and engineering whose leadership and impact echo Millie’s life, accomplishments, and values.

Evolving organisms to grow new nanomaterials for energy, the environment, and medicine

Angela Belcher, PhD

James Mason Crafts Professor
Biological Engineering, Materials Science and Engineering, and the Koch Institute for Integrative Cancer Research, MIT

Monday, November 20, 2023
4:00 PM – 5:00 PM EST
MIT Bldg 10, Room 250

About Angela Belcher's lecture

Organisms have been making exquisite inorganic materials for over 500 million years. Although these materials have many desired physical properties such as strength, regularity, and environmentally benign processing, the types of materials that organisms have evolved to work with are limited. However, there are many properties of living systems that could be potentially harnessed by researchers to make advanced technologies that are smarter, more adaptable, and that are synthesized to be compatible with the environment.

One approach to designing future technologies that have some of the properties that living organisms use so well is to evolve organisms to work with a more diverse set of building blocks. The goal is to have a DNA sequence that codes for the synthesis and assembly of any inorganic material or device.

We have been successful in using evolutionarily selected peptides to control physical properties of nanocrystals and subsequently use molecular recognition and self-assembly to design biological hybrid multidimensional materials. These materials could be designed to address many scientific and technological problems in electronics, environmental remediation, medicine, and energy applications. Currently we are using this technology to design new methods for building batteries, fuel cells, solar cells, carbon sequestration and storage, environmental remediation, catalysis, and medical diagnostics and imaging.

This talk will address conditions under which organisms first evolved to make materials and scientific approaches to move beyond naturally evolved materials to genetically imprint advanced technologies with examples in lithium and sodium ion batteries, lithium-air batteries, environmental clean-up, and ovarian cancer imaging and treatment

32nd Annual Irwin M. Arias Symposium

The first Irwin M. Arias, M.D. Symposium was held in 1991, and the theme of the event was – as it remains today – Bridging Basic Science and Liver Disease.

This unique one-day program brings together hundreds of leading biomedical scientists and physicians from across the globe and is designed to bridge the remarkable advances in basic biology and engineering with the understanding of liver diseases and their treatment. Research presented over the past 32 years has led to advances in the diagnosis and treatment of virtually all liver diseases in children and adults.

With plenary talks from renowned researchers and a collection of three-minute micro talks delivered by trainee scientists, the Arias Symposium is a model in ‘bridging’ between the academic, industrial, and clinical research communities – even across disciplines.

Historically, the Arias Symposium has been an in-person event until the pandemic caused a shift to a virtual format. For 2023, the symposium will be offered both in-person and virtually. Registration is free.

We welcome participation from researchers at every stage of their careers, and invite them to share perspectives from their academic, industrial, and clinical research settings. Trainees and early-career investigators who are interested in presenting a micro-talk (in-person or virtually) or poster (in-person only), should submit an abstract with their registration. The deadline to submit an abstract has been extended to November 3, 2023.

SPATIAL BIOLOGY LUNCH AND LEARN SYMPOSIUM CO-HOSTED BY LEICA MICROSYSTEMS AND THE MARBLE CENTER FOR CANCER NANOMEDICINE

Join the Leica team and other MIT researchers to explore the latest technologies and research that utilize spatial mapping to uncover molecular insights in oncology, neurology, and immunology. Together with leading experts, we will examine how a deeper understanding of the tissue microenvironment, using advanced imaging techniques, can shed new insights into diseases such as metabolic disorder and cancer.

Speakers:

Intercepting Ovarian Cancer

Thursday, November 2, 2023, 3:00 p.m.

Luria Auditorium, Koch Institute
500 Main Street, Cambridge, MA

Koch Institute Professors Angela Belcher, Sangeeta Bhatia, and Paula Hammond will present their multi-dimensional approaches to tackling the challenge of early detection in ovarian cancer and their technologies that could identify new ovarian cancer biomarkers. They will be joined by MIT alumna Parul Somani, who will share her experiences as a BRCA1 carrier, breast cancer survivor, ovarian cancer previvor, and cancer care-giver. A dessert reception in the KI Public Galleries will follow.

The 2023 Lippard Lecture

Christina Curtis, PhD, MSc, has been selected as the recipient of the 2023 Judith Ann Lippard Memorial Lectureship. Dr. Curtis is Professor of Medicine, Genetics & Biomedical Data Science at Stanford University School of Medicine, where she is a Director of the Artificial Intelligence and Cancer Genomics and Director of Breast Cancer Translational Research. She will present her lecture, "Forecasting and exploiting tumor-host interactions," to the MIT and Koch Institute communities in the Luria Auditorium (76-156) on Friday, October 27. 

Dr. Curtis leverages computational modeling, high-throughput molecular profiling and experimentation to develop new ways to prevent, diagnose and treat cancer. Her research has redefined the molecular map of breast cancer and led to new paradigms in understanding how human tumors evolve and metastasize.

THE NANO SUMMIT

October 24, 2023

MIT.nano will celebrate its 5th anniversary with The Nano Summit! The first of an annual flagship conference for MIT.nano, this event will highlight the astonishing research being done at MIT and look to the future of nanoscience and engineering

Marble Center Distinguished Seminar Series

Giovanni Traverso, MD, PhD

July 17, 2023 4-5pm (Koch Institute Luria Auditorium)

Giovanni Traverso is an Associate Professor in the Department of Mechanical Engineering at the Massachusetts Institute of Technology (MIT) and also a gastroenterologist in the Division of Gastroenterology, Brigham and Women’s Hospital (BWH), Harvard Medical School. Dr. Traverso grew up in Peru, Canada and the United Kingdom.  He received his BA from Trinity College, University of Cambridge, UK, and his PhD from the lab of Prof. Bert Vogelstein at Johns Hopkins University.  He subsequently completed medical school at the University of Cambridge, internal medicine residency at the Brigham and Women’s Hospital and his gastroenterology fellowship training at Massachusetts General Hospital, both at Harvard Medical School. Dr. Traverso’s previous work focused on the development of novel molecular tests for the early detection of colon cancer. For his post-doctoral research, he transitioned to the fields of chemical and biomedical engineering in the laboratory of Professor Robert Langer at MIT where he developed a series of novel technologies for drug delivery as well as physiological sensing via the gastrointestinal tract.

His current research program is focused on developing the next generation of drug delivery systems to enable safe and efficient delivery of therapeutics, biomedical device to support new modes of drug administration and sensing a broad array of physiologic and pathophysiologic signals. Additionally, Dr. Traverso continues his efforts towards the development of novel diagnostic tests that enable the early detection of cancer.

SAVE THE DATE

Special seminar: Dr. Minh Le, National University of Singapore

Delivery of nucleic acid therapeutics using extracellular vesicles from red blood cells.

Tuesday May 23, 3-4pm (Koch Institute Luria Auditorium)

Abstract: Despite their promise of therapeutic potency, many applications of nucleic acid-based drugs are currently limited by the poor delivery efficiency. As an emerging delivery platform for nanomedicine, extracellular vesicles (EVs) exhibit various advantageous features, including low immunogenicity and high biocompatibility. Moreover, the lipid bilayer that delimits each EV not only protects the nucleic acid cargo within but also displays a variety of biomolecules that may be modified to improve delivery performance. EVs can be produced in large quantities from primary red blood cells (RBCs) at relatively low costs. Leveraging these strengths, our group have worked with collaborators and industry partners to develop and validate an efficient method of loading nucleic acids into RBCEVs using the REGENT® platform. Importantly, we have successfully conjugated peptides and antibodies to therapeutically loaded RBCEVs for targeted delivery. We have employed these technologies to deliver RIG-I agonists as immunotherapy to suppress breast cancer and its metastasis to the lungs. We are also exploring the use of RBCEVs to deliver small interfering RNAs to alleviate cancer cachexia and antisense oligonucleotides to treat COVID-19, with encouraging data in cell and mouse models. The feasibility of loading these different nucleic acids that target different diseases highlights the versatility of the RBCEV platform and suggests its future development for diverse applications.

Bio: Dr. Le graduated from the National University of Singapore in 2005 with a bachelor’s degree in Life Sciences. She further received a Ph.D. degree in Computational and Systems Biology from the Singapore-Massachusetts Institute of Technology (MIT) Alliance under the guidance of Prof. Bing Lim at the Genome Institute of Singapore and Prof. Harvey Lodish at the Whitehead Institute for Biomedical Research. From 2010 to 2015, she took a postdoctoral training under Prof. Judy Lieberman at Boston Children’s Hospital and Harvard Medical School in the USA. From 2015 to 2019, she worked as an Assistant Professor at the Department of Biomedical Sciences at City University of Hong Kong (CityU). She became a tenure-tracked Assistant Professor at Department of Pharmacology, National University of Singapore, in 2019.

Dr. Le is well recognized for her contributions to the field of microRNAs (miRNAs), extracellular vesicles (EVs) and cancer biology. She was the first to identify a miRNA that regulates p53, an important tumor suppressor gene. This miRNA, miR-125b, was subsequently found to be a potent oncogenic miRNA in leukemia and many solid tumors. Dr. Le characterized the anti-apoptotic functions of miR-125b in zebrafish embryos and mammalian cells. She demonstrated that this tiny RNA is dispensable for normal development as it regulates the delicate balance between cell death and growth by repressing the p53 gene network. Furthermore, during her postdoctoral training, Dr. Le illustrated a novel mechanism of cancer crosstalk in which miRNAs secreted by metastatic breast cancer cells are delivered to non-metastatic cells via extracellular vesicles (EVs) and promote colonization of tumor cells in the lung. Recently, our group has established a new EV-based drug delivery platform with efficient and safe delivery of RNA drugs to cancer cells. With these original findings, Dr. Le’s articles have been cited over 2,000 times by researchers worldwide (link).

In addition to her interest in research, Dr. Le also has a passion in education. She has organized the translation of “Molecular Cell Biology”, an American biology textbook by Lodish et al., into Vietnamese. As the project coordinator for the last 10 years, she has brought together the American authors, Vietnamese scholars, publishers, sponsors and hundreds of backers, to translate the most advanced knowledge in biology and promote science education in Vietnam. The book has been warmly welcomed by scientists and biology students in the country (link). Dr. Le also co-organized the Hong Kong RNA club for education in RNA research (link) and the EV journal club at the Singapore Society for clinical, research and translation of EVs (SOCRATES).

Dr. Le was awarded several prestigious scholarships and fellowships during her studies such as the Lee Foundation study grant and the Singapore-MIT Alliance scholarship. She was one of the first three recipients of the L’Oréal Singapore for Women in Science National Fellowship broadcasted widely by the news in 2009 (link). During her training at Harvard Medical School, she was awarded the Jane Coffin Childs fellowship, a prestigious postdoctoral fellowship in the USA. She also won a number of competitive travel scholarships and poster awards at international conferences. As an independent investigator, she has won various competitive external grants in Hong Kong and Singapore.

Dr. Le is currently an associate editor of the Journal of Extracellular Vesicles (JEV) and a deputy editor of the Journal of Extracellular Biology (JEB). She is also a scientific co-founder and advisor of Carmine Therapeutics (link), a start-up company based on red blood cell EVs, based in Singapore and Boston. Carmine Therapeutics has raised more than 10M USD seed funding and recruited about 20 employees. It was considered one of the top 15 biotech start-up companies in 2020.

Marble Center for Cancer Nanomedicine Annual Poster Symposium

OPEN ONLY TO MIT AND MEMBERS OF THE MARBLE CENTER INDUSTRY PROGRAM

The 2023 Marble Center for Cancer Nanomedicine poster symposium will convene members of the Koch Institute for Integrative Cancer Research and broader MIT community working on nano- and precision based approaches for the early detection and treatment of cancer.

The event will be held at the Koch Institute Luria Auditorium. This will be an in-person only event, and will be an excellent opportunity to highlight collaborative projects in this area and get feedback from faculty and industry members.

Please register by April 28th so that we can get an accurate count for displays and catered food.

Represented industry partners: Alloy Therapeutics, Danaher Corp., FUJIFILM, and Sanofi.

SOLUTIONS with/in/sight: Algorithm and Views

Thursday, May 4, 2022
6:30 p.m.

Luria Auditorium, Koch Institute
500 Main Street, Cambridge MA

Two teams of KI investigators share their innovations using machine learning tools to improve lung cancer detection. Coupling machine learning algorithms with responsive nanoparticles, KI alum Ava Amini and Jesse Kirkpatrick of the Bhatia Lab develop noninvasive diagnostics to classify tumor types and inform patient interventions. They are joined by KI computer scientist Regina Barzilay and oncologist Lecia Sequist who will discuss how they use algorithms to look deeper into radiology images to predict future cancer risk. Through these projects, the researchers present their vision for smarter decision-making and better care for patients.

These projects were supported in part by the Koch Institute Frontier Research Program and the Bridge Project, respectively

8th Annual Non-coding RNA Symposium sponsored by the HMS Initiative for RNA Medicine and the Cancer Center at Beth Israel Deaconess Medical Center.

SOLUTIONS with/in/sight: Anchor Management

Tuesday, April 4, 2022
6:30 p.m.

Luria Auditorium, Koch Institute
500 Main Street, Cambridge MA

Immune engineers Darrell Irvine and K. Dane Wittrup join Ankyra Therapeutics CEO Howard Kaufman to discuss the evolution of a convergent bench-to-bedside collaboration that uses localized cytokine therapy to awaken a powerful immune response against solid tumors. The company's anchored immunotherapy approach grew directly out of two independent Koch Institute research projects and is expected to begin clinical trials in 2023. Immunologist Stefani Spranger provides an introduction to cancer immunotherapy.