BOSTON- The Sean M. Healey & AMG Center for ALS is thrilled to announce the 2024 MGH ALS Young Investigator Awards. These awards celebrate the work of researchers and innovators in the field of ALS research.

2024 Byrne Family and Judith & Jean Pape Adams Endowed Fellowship

Ayub Boulos, Ph.D., for Elucidating how STMN2 loss in ALS leads to disruption of axonal transport and denervation of the neuromuscular junctions.

Dr. Boulos and the group from the lab of Dr. Clotilde Lagier-Tourenne focus their research efforts on the RNA binding protein TDP-43 and the neuronal growth-associated protein Stathmin-2. Their recent work has shown that reduction in the levels of STMN2 protein upon TDP-43 depletion impairs axons regeneration capacity after axotomy and lysosomal axonal transport in human iPSC-derived motor neurons. Dr. Boulos will investigate the impact of STMN2 loss on the axonal transport of organelles and RNAs, and use state-of-the-art spatial proteomics to determine how STMN2 reduction affect the protein composition of axons and neuromuscular junctions. This research will provide invaluable insights on the contribution of STMN2 loss in the disruption of axons and neuromuscular junctions in ALS.

2024 Corcoran Family Award

Doreen Ho, M.D.

Dr. Ho is the ALS Clinic Director in the Division of ALS and Motor Neuron Diseases at the Sean M. Healey & AMG Center at Massachusetts General Hospital and an Assistant Professor of Neurology at Harvard Medical School. She joined Mass General Neurology as faculty in 2021 and serves as the Program Director of Education for the Division of ALS and Motor Neuron Diseases. Dr. Ho previously served as Director of the Lahey ALS Clinic at Tufts University/Lahey Health. Since her arrival at Mass General, she has built an adult multidisciplinary SMA clinic which currently serves patients with SMA, offers multidisciplinary care, leading RNA-targeted therapies, and key clinical research. This award will provide valuable support for the work that Dr. Ho is leading in ALS clinical care innovation and clinical research trials.

2024 Mussallem Transformative Scholars

Aaron Held, Ph.D.
Aaron Held, Ph.D.,
for Elucidating the molecular mechanisms that cause and mitigate TDP-43 pathology

Dr. Held’s research focuses on pathological TDP-43 aggregates and how they arise and contribute to neurodegeneration. He has identified several genes that are misregulated in ALS or Alzheimer's disease that also contribute to disrupted TDP-43 regulation. Furthermore, he has identified several compounds that help restore normal TDP-43 localization in human iPSC-neurons. Over the course of his young investigator award, Dr. Held will further elucidate the molecular mechanisms linking these misregulated genes to TDP-43 pathology and determine whether these compounds should be pursued for further development as therapeutic targets.

Christine Marques, Ph.D.

Dr. Marques and team have focused their research on the intronic expansion of the C9ORF72 gene as the most common familial ALS variant and a major contributor to sporadic ALS. This proposal aims to validate the relevance of Dr. Marques’ past findings of using synthesized dipeptide repeat proteins to mimic a component of C9orf72 toxicity and cellular stress assays, that capture features of TDP-43 pathology in vivo, by assessing the therapeutic efficacy of an FDA-approved compound in a C9orf72 dipeptide repeat mouse model. Additionally, through RNA sequencing and CRISPR-mediated gene editing technology the study will identify the best target genes in the molecular pathways affected by the hit compounds. This approach will establish multiple approaches for therapeutic intervention in ALS, including the identified FDA-approved drug, gene target-based approaches such as antisense oligonucleotides on pathway components, as well as new small molecule development for druggable targets.

Jing Cai, Ph.D., for Neural Mechanisms Underlying Social Communication in Humans

Dr. Cai’s proposal aims to directly explore neural representations in natural human conversations, leveraging intracranial sEEG recordings with millisecond temporal resolution across diverse brain areas and cutting-edge Large Language Models (LLMs) as a powerful representational model. Ultimately, this study will help to begin to uncover some of the basic neural underpinnings of linguistic and social cues within the broad field of human communication. Results of this study will have a broad impact to benefit individuals with social deficits or language impairments, including conditions like ALS and neurodegenerative disease, and provide insights to the impact of novel technology-based communication on social engagement.

Tiziana Petrozziello, Ph.D.,
for Targeting tau to promote innervation at the neuromuscular junction in amyotrophic lateral sclerosis.

Dr. Petrozziello’s recent studies have demonstrated that tau phosphorylation (pTau) is increased in ALS post-mortem brain and causes oxidative stress. Importantly, degrading pTau with a selective degrader reduced oxidative stress, suggesting that targeting pTau may be a potential therapeutic target for ALS. Dr. Petrozziello’s latest findings show that pTau is increased in human post-mortem muscle as well as in muscle derived from the SOD1G93A animal model of ALS, suggesting that pTau may also play a role in peripheral tissues. Therefore, the team’s hypotheses are that (a) pTau accumulates at the NMJ in ALS and causes muscle denervation, and (b) reducing pTau at the NMJ could improve regeneration of axons and increase innervation of the NMJ, thereby improving motor function in ALS. These studies are innovative and may identify a peripheral target to reverse denervation and restore motor function in ALS.

About the Sean M. Healey & AMG Center for ALS at Mass General

At the Sean M. Healey & AMG Center for ALS at Mass General, we are committed to bringing together a global network of scientists, physicians, nurses, foundations, federal agencies, and people living with ALS, their loved ones, and caregivers to accelerate the pace of ALS therapy discovery and development.

Launched in November 2018, the Healey & AMG Center, under the leadership of Merit Cudkowicz, MD and a Science Advisory Council of international experts, is reimagining how to develop and test the most promising therapies to treat the disease, identify cures and ultimately prevent it.

With dozens of active clinical trials and lab-based research studies in progress right now, we are ushering in a new phase of ALS treatment and care. Together, we will find the cures.