Transformative Research in Rare Diseases: 2020 Innovators in Science
By definition, a rare disease is one that afflicts relatively few people compared to the general population. Collectively, though, there are over 7,000 of these conditions known, causing immense suffering for an estimated 300 million patients. Because most rare diseases stem from specific genetic mutations, they’ve proven difficult to treat.
Genome sequencing and molecular medicine might soon change those grim statistics, though. For example, using short DNA or RNA sequences complementary to the messenger RNA for a gene, researchers can inhibit the expression of the associated protein. These complementary sequences—called antisense oligonucleotides—could soon be delivered as drugs to treat many rare diseases.
On October 2, 2020, the New York Academy of Sciences and Takeda Pharmaceuticals hosted Frontiers in Rare Diseases: 2020 Innovators in Science Award Symposium, an event highlighting breakthroughs in rare diseases research and honoring 2020 Innovators in Science Award Winners Adrian Krainer, Ph.D., and Jeong Ho Lee, M.D., Ph.D. Presentations, a panel discussion, and a virtual poster session covered the basic science, recent clinical breakthroughs, and remaining challenges in this rapidly evolving field.
- While many rare diseases are inherited, others arise through mutations in somatic cells during life.
- Antisense oligonucleotides can alter the expression of specific genes, potentially mitigating or reversing many genetic diseases.
- Clinical trials for rare disease therapies must be tailored to the pathogenesis of each disease.
- Redirecting neural stem cells to become neurons could treat many neurodegenerative diseases.
- The COVID-19 pandemic is inspiring new collaborations that could be adapted to rare disease research.
New Therapeutic Strategies to Treat Metastatic Cancer
Metastatic cancer occurs when cancer cells migrate from the primary tumor and invade other tissues and organs within the body. The systemic effects of metastatic cancer, which include vascular remodeling, alterations in cellular metabolism, and changes to the immune system, make it particularly challenging to treat. Current therapies aim to slow or halt tumor progression, but often fail to eradicate cancer. On October 21-22, 2020, the New York Academy of Sciences hosted the Systemic Effects of Metastatic Cancer symposium. Cancer research experts shared their work leveraging cell biology, immunology, genomics, microbiology, and more to improve our understanding of metastatic cancer and develop novel treatment strategies. Read on to learn about the latest advances in metastatic cancer research.
- BIRC2 expression reduces anticancer immunity in melanoma and breast cancer.
- The premetastatic window upregulates immunosuppressive genes.
- Microbiome modulation reduces tumor growth in metastatic colorectal cancer.
- Sympathetic nerve signals are critical for tumor initiation in prostate cancer.
- IL11 is a non-cell autonomous driver in breast cancer.
- CREB pathway suppression prevents brain metastases in mice with lung cancer.
- Breast cancer mouse models “dosed” with exercise exhibit reduced metastases.
- Redox metabolism suppresses metastasis in skeletal muscle.
Immune Mechanisms and Therapeutic Advances in Heart Failure
According to the Centers for Disease Control and Prevention, heart failure affects about 6.2 million adults in the U.S. Although heart failure has been well studied, the links between heart failure, inflammation, and immune system activation are still unclear. Over the past few decades, research interest in this topic has grown and highlighted the important role of the immune system in cardiac function. On October 27, 2020, the New York Academy of Sciences hosted a virtual symposium with speakers who bridge the gap between cardiology and immunology. They discussed the post-myocardial infarct immune system, hypertension-induced cardiac inflammation, macrophages and their role in ischemic and non-ischemic heart failure, and the anti-inflammatory hypothesis.
- Inflammatory responses impact valvular carditis, atrial fibrillation, and heart failure progression.
- Sex differences play a role in the viral causes of cardiac inflammation, including COVID-19.
- Macrophages affect tissue homeostasis, and specific macrophage populations may be expressed in diseased hearts.
- Elevated CaMKIIδ, prior cardiac episodes, and various cancers are all linked to increased risk of cardiovascular diseases.
- New technologies proposed for the future include improved imaging techniques with inflammatory biomarkers and potential therapeutics with CAR T cells to treat cardiac fibrosis.
- The connection between irreversible heart failure, unresolved tissue damage, and chronic inflammation has enhanced our understanding of the innate and adaptive immune systems in the pathogenesis of heart failure.
Is a Traditional College Degree Still Worth It?
The current pandemic has reignited the conversation about the value of a traditional four-year college degree. The need to socially distance has accelerated the adoption of remote learning, bringing to a head long-standing questions about access, cost, and overall value of higher education. With the rise of unemployment, universities must also reimagine ways to help students transition to the workforce while still offering a well-rounded education. The New York Academy of Sciences hosted a panel to discuss the role of higher education in society, how the pandemic is forcing schools to push the boundaries of the learning experience, and the transformational changes that may result from these challenges.
- Questions about the scalability and affordability of higher education have resurfaced as a result of the shift to online instruction during the pandemic.
- The on-campus component of college life, a valuable part of the learning experience, is hard to replicate online; colleges and universities must reimagine ways to help students connect and acquire hands-on experience in the digital era.
- Traditional college degrees are still the most valuable credential in the job market, but employers are increasingly open to alternatives such as certificates or boot camps.
- Is the role of universities to produce engaged citizens or skilled workers? By nurturing soft skills and helping students connect their academic interests with a meaningful mission, higher education may be able to play both roles simultaneously.
Linking Metabolism, Health, and Cancer: 2020 Dr. Paul Janssen Award Symposium
Lewis C. Cantley’s discovery of the enzyme phosphatidylinositol-3-kinase (PI3K) paved the way for a better understanding of cellular metabolism and its role in human diseases. In response to insulin, PI3K signals through lipids to activate a cellular cascade resulting in increased glucose uptake and subsequent cell growth and division. Cantley’s work has led to new cancer therapies, as PI3K pathway mutations are among the most common to drive cancer development, and a better understanding of insulin resistance in diabetes.
For his groundbreaking discovery of PI3K and critical body of research, Lewis C. Cantley, Ph.D., of Weill Cornell Medical College, received the 2020 Dr. Paul Janssen Award for Biomedical Research. On September 16, 2020, the New York Academy of Sciences hosted the award symposium to celebrate his achievements. Following Cantley’s award lecture, other experts in the field shared their work on the intersection between cellular metabolism, biology and disease.
- Differences in cell metabolism across cancer types may help explain why cancer cells are differentially sensitive to drugs that target metabolism.
- The tumor suppressor protein p53 regulates several pathways that manage the production of reactive oxygen species in the mitochondria.
- Metabolic pathways are a powerful, and to-date, underappreciated set of therapeutic targets for cancer.
- Drugs that regulate metabolic pathways involved in cell differentiation are promising targets for acute myeloid leukemia.
- Cancer researchers are coming to appreciate how a patient’s diet can be therapeutically applied and may directly modulate their disease progression and therapeutic response.
Discovering New Drugs to Treat Chronic Kidney Disease
Chronic kidney disease (CKD) affects over thirty million Americans and more than 800 million people worldwide, making it a significant public health problem. Despite its prevalence, CKD lacks effective therapeutics with patients requiring dialysis or kidney transplants to survive. Variable genetic and environmental factors influencing disease development further complicate treatment. On September 25, 2020, the New York Academy of Sciences hosted the Drug Discovery for Remission of Chronic Kidney Disease symposium. Leaders in precision medicine, genomics, imaging technology, transplantation, and entrepreneurship shared their work toward advancing our understanding of kidney disorders and developing novel treatment strategies for CKD. Read this summary to learn more about the latest advances in kidney disease research.
- Kidney Atlas aims to advance pathology and identify new therapeutics.
- Lyfebulb empowers innovation by bridging the gap between chronic disease patients and the healthcare industry.
- Kidney Risk Inflammatory Signature (KRIS) protein biomarkers predict diabetic kidney disease.
- Kidney organoids derived from patient urine cells provide personalized disease insight.
- Multi-omics approaches identify genetic drivers of CKD.
- Novel imaging method can visualize individual nephrons in vivo.
- Recipients tolerate kidney transplantation with apoptotic donor cells.
- SGLT2 inhibitor drugs lower the mortality rate for CKD patients.
- Whole exome sequencing diagnoses CKD cases of unknown origin.
Linking Neuroscience and Mindfulness
Meditative practices that cultivate mindfulness are a foundational element of Buddhist teachings. For centuries, those practices have been experienced as an antidote to human suffering. However, scientific research into the effects of mindfulness on health, and how its cultivation might affect the body, overall well-being, and even longevity is very recent. In this e-Briefing, four leaders in the field explain what mindfulness is and what happens in our brains when we meditate. They discuss the latest research on meditation’s effect on mental and physical health and give practical advice on how meditative practices could be used to cope with elevated stress levels during these uncertain times.
- Mindfulness is defined as a nonjudgmental moment-to-moment awareness. It can be accessed and sustained through different modes of meditative practices.
- Mindfulness meditation positively affects multiple neuronal networks in the brain.
- Several scientific studies have shown that mindfulness practices can reduce stress and anxiety, increase attention, and elevate mood.
- Researchers are still investigating the likely mechanisms of meditations’ beneficial effects on health. Potential targets are epigenetic and anti-inflammatory pathways.