It has been well established that mental health goes hand in hand with physical health. Living with a chronic condition places a daily emotional strain on both patients and caregivers. For those with a rare disease, the situation is exacerbated by unique challenges, including longer time to diagnosis; more frequent misdiagnoses; few, if any, available treatments; and often complex care. This greater mental load, accompanied by the physical challenges that come with a rare disease, has profound psychological implications. In addition, there are intractable well-being issues around genetic testing that need to be addressed, in concert with the real possibility of genetic therapies in the near future. How can these realities be compassionately and sensitively discussed, and how might they impact the way patients think about their medical condition? In this webinar, we examine these issues and address how physicians and the medical community can better support those living with a rare disease as well as their caregivers.

This webinar will last for approximately 60 minutes.

As our knowledge of the intricate workings of the human nervous system has grown, so has our ability to modulate its activity using precisely targeted, externally generated signals. Together with this increased knowledge have come advances in technology—particularly in miniaturization, wireless communication, and battery-power density—that have enabled the engineering of sophisticated implantable devices to control neural activity. This rapid progress in the field of neuromodulation has presented new opportunities for its application in treating debilitating disorders such as Parkinson’s disease, epilepsy, chronic pain, and depression. More recently, neuromodulation techniques have been used to successfully address the many challenges faced by limb amputees, including phantom-limb pain and limited proprioception in their prosthesis. In neuromodulation modalities that directly stimulate brain neurons, one of the biggest challenges is accurate targeting of the correct cells or cell clusters. Experiments using three-dimensional holographic optogenetics—a recently developed technique that applies two-photon light to stimulate neurons more precisely than is possible with physical electrodes—have achieved spatial specificity at cellular resolution. Although currently limited to animal models, this breakthrough holds enormous promise to eventually provide physiologically relevant neuromodulation of the brain.

In this webinar, we will discuss the development and application of these technological advances and their potential to profoundly improve the quality of life of patients with neurological challenges.

During the webinar, the speakers will:

• Present their latest work on neurotechnologies for peripheral nervous system interfacing and 3D holographic optogenetics for brain stimulation
• Discuss the translation of neuromodulation advances to the clinic, including the primary hurdles that need to be overcome
• Examine the future of these and other neuromodulation techniques for the treatment of disease and the enhancement of patient well-being.

This webinar will last for approximately 60 minutes.

SARS-CoV-2 infection may cause acute respiratory disease and, in some patients, result in multiorgan failure. In-depth understanding of its disease pathophysiology and the underlying reasons for interpatient symptom variability are still lacking. A collection of over 450 specimens of various organs—including lung, heart, kidney, and liver—from 17 autopsies of patients who suffered severe COVID-19 infection, combined with single-cell and single-nuclei gene-expression measurements and complementary spatial transcriptomics strategies, was used to generate single-cell atlases of these tissues to better understand the progression of this disease. The results revealed disease mechanisms associated with lung-tissue remodeling and multiple failed pathways in epithelial-cell regeneration. Specific cell populations that are enriched in viral RNA, implying specific viral targets in the lung, were identified. Mapping of genes associated with COVID-19 severity from genome-wide association studies (GWAS) to the cell atlases showed which cell populations these genes were upregulated in. Two novel single-cell genomics computational methods—one that automatically annotates cell types based on previously published and unpublished lung datasets, and the other that corrects expression for ambient RNA prevalent in the necrotic tissues collected—were also used to create these atlases. This cohort is a unique and versatile resource for studying COVID-19 in severe patients, including samples from multiple organs of the same donor. This foundational dataset helped elucidate some of the biological effects of severe SARS-CoV-2 infection across the body, which is a key step toward development of new treatments.

Dr. Rachelly Normand, a computational postdoctoral associate in the laboratories of Alexandra-Chloé Villani and Peter Kharchenko from Massachusetts General Hospital, Harvard Medical School, and the Broad Institute, will:

• Present an overview of the single-cell, single-nuclei, and spatial transcriptomic atlases collected from COVID autopsy donors, including from the lung, heart, kidney, and liver
• Describe possible COVID-19 disease mechanisms in the lung derived from single-cell RNA-sequencing data, such as failure of lung regeneration and cellular targets of viral infection
• Elaborate on two novel computational methods for single-cell data preprocessing—the first for automatic cell annotation and the second for correction of ambient RNA in single-cell RNA
• Answer your questions live during the broadcast.

This webinar will last for approximately 60 minutes.