Our Projects

HCU Network Australia together with HCU Network America are pleased to announce their first Research Grant was awarded in 2018. The HCU Network Australia Grant is made possible by people within our community who raise funds on our behalf.  HCU Network Australia thanks the community first and foremost for making these Grants possible.  The HCU Network America Grant is through the Hempling Foundation for Homocystinuria Research, established in memory of Judy and Susie Hempling, two young girls from Buffalo, NY whose lives were cut short by HCU in the 1970s.

The HCU Networks extend a warm thanks to our Scientific Advisory Board for generously giving their time and expertise to review the Research Grant Applications and a special thanks is extended to the independent reviewers of these Applications for their valuable insight and expertise in their evaluation of the Grant Applications.

You can read more about our Research Strategy and Research Grants program.

The HCU Networks plan to continue this Grant Program through issuing calls for Expressions of Interest on a periodic basis. The next call is planned first half of 2021.

  • Project Title: Development of Reference Ranges for Additional Newborn Screening Markers for Early Detection of the Homocystinurias: Classical Homocystinuria and Remethylation Disorders
  • Principal Investigator: Devinder Kaur, PhD
  • Amount: $10,000
  • Status: Active
August 31, 2022 - HCU Network America announced the recipient of their first newborn screening research grant. The New England Newborn Screening Program, an initiative of UMass Chan Medical School’s Commonwealth Medicine division, received the award to explore the development of reference ranges for additional newborn screening markers for early detection of classical homocystinuria and remethylation disorders.  The research, led by Devinder Kaur, PhD, assistant professor of pediatrics at UMass Chan, aims to establish normal reference ranges for total homocysteine, along with other analytes collected by healthy newborns during the 24-48 newborn screening period. This will support the development of algorithms that will incorporate information on a variety of other variables in the future. Dr. Kaur, who is leading the research, joined the New England Newborn Screening Program in 2017 as a senior scientist.


Dr. Kaur, who is leading the research says “I am extremely honored and happy to receive this grant from HCU Network America, as this builds on our previous and current work to improve and expand screening methods for the homocystinurias using tandem mass spectrometry with the ultimate goal to help prevent treatable disorders through early detection. This project will leverage the New England Newborn Screening Program’s technical and clinical expertise along with the UMass Chan infrastructure that provides access to screening for a wide variety of disorders; by identifying markers, developing assays, and by generating data, algorithms and protocols that could be adopted nationwide in screening for medically relevant conditions. On behalf of the New England Newborn Screening team, I would like to express my sincere gratitude to HCU Network America for their generous support”.

Dr. Harvey Levy, a newborn screening pioneer and HCU Network America board member said, “We are pleased to fund this grant to develop reference ranges for analytes measured in newborn screening that are markers for the homocystinurias and remethylation disorders, which will further support the adoption of two tier testing to improve the sensitivity of newborn screening and enable these infants to be diagnosed at birth and given the best chance of leading healthy and productive lives”.

You can read the full press release here


Devinder Kaur, PhD

Dr. Kaur is an assistant professor in the department of pediatrics at the UMass Chan Medical School. She received her master’s and PhD from the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She was a Research Scientist at the Colorado state University, Fort Collins, Colorado where she used an integrated approach of biochemistry, bioinformatics and genetics to decipher biosynthetic pathways of the mycobacterial cell wall with a view to new drug development and vaccine candidates for the treatment of tuberculosis. At Massachusetts Supranational TB Lab, she led activities ranging from providing technical assistance and technology transfer to developing countries, designing and implementing quality assurance systems, and drug potency testing, as well as practical and didactic training in diagnostic methods and quality assurance. She also participated in several operational research projects with academic research institutions and molecular diagnostic companies to identify mechanisms of drug resistance and to validate new diagnostic tests. She authored and co-authored articles in peer reviewed journals, on basic and operational research in the area of infectious diseases and newborn screening.

Dr. Kaur joined the New England Newborn Screening Program (NENSP) in 2017 as a senior scientist. She has served several roles and made strong contributions to various scientific and administrative operations of the program including the validation and implementation of a new Laboratory Information Management System, the program’s short term follow-up responsibilities, optimization and implementation of a Covid antibody assay for a special collaborative epidemiological project and to the day-to-day clinical laboratory QC and troubleshooting activities of the metabolic laboratory. She is now leading the design, development and validation of improved and new mass spectrometry-based assays.

  • Project title: Crystallography-based fragment screening to develop pharmacological chaperones for classic homocystinuria
  • Principal Investigator: Thomas McCorvie, PhD
  • Amount: $USD 40,000
  • Status: Active
HCU Network America have announced the third recipient of the CBS deficiency global grants program – awarding a research grant to the Newcastle University Biosciences Institute in Newcastle, United Kingdom to explore a potential avenue for treatment for homocystinuria due to cystathionine beta-synthase (CBS) deficiency. The research, led by Dr. Thomas McCorvie, aims to identify stabilizers or activators of the defective enzyme in CBS-deficient homocystinuria (HCU). Dr. McCorvie is a Senior Research Associate at the Newcastle University Biosciences Institute

“Inherited mutations of Cystathionine Beta-Synthase (CBS) enzyme result in reducing its activity by destabilization and aggregation. There is precedent that small molecules which specifically bind to and stabilize CBS could restore mutant CBS activity by acting as a pharmacological chaperone (PC). Therefore, this project aims to screen for small molecules that bind to and stabilize CBS using fragment-based x-ray crystallography screening (XChem). XChem involves crystallizing the CBS protein hundreds to thousands of times and then soaking each crystal with a large library of fragments. Any small fragments that bind to CBS will be identified using x-ray crystallography and used as starting points to develop into larger molecules.”, said Dr. McCorvie.

“These potential binders will then be triaged against CBS and its disease mutants to determine if they act as PC molecules rescuing their functionality. The most promising small molecules can then be possible starting points for further preclinical studies in cell lines and animal models, and if successful can be developed as a PC therapy for classical homocystinuria.

I am incredibly honoured and excited that our proposal has been funded by the HCU Network America, as this builds on our previous work on the structural biology of CBS along with our goals to develop novel therapies for rare metabolic disorders. As such this research will leverage our group’s multi-disciplinary experience in biophysics, biochemistry, and structural-based drug screening along with guidance from our clinical contacts in the homocystinuria field.”

“We are pleased to support this research project to build upon the previous work on the crystal structure of the CBS enzyme by Drs. McCorvie and Yue, and we are hopeful that potential chaperone therapies can result from their work and be further developed into new treatments to support our patient community.” said Margie McGlynn, President of HCU Network America.

You can read the full press release here

Thomas McCorvie, PhD

McCorvie earned his BSc in biochemistry at Queen's University Belfast 2008, after where he was awarded a PhD in 2012 based on his work on the biochemical basis of galactosemia with Prof. David Timson. In 2012 he began a postdoctoral position in Prof Wyatt Yue's lab at the University of Oxford. During that time, he developed skills in x-ray crystallography of metabolic proteins involved in rare diseases with a focus on cystathionine beta-synthase (CBS). In 2016 he accepted a postdoctoral position in Prof Xiaodong Zhang's lab at Imperial College London where he further developed structural biology skills using cryo-electron microscopy (cryo-EM) towards the aim of solving structures of large protein complexes involved in DNA repair. In 2019 he returned to the lab of Prof Wyatt Yue and in 2021 was promoted to senior research associate at Newcastle University where he uses his experience to determine structures of enzyme complexes involved in carbohydrate and amino acid metabolism.  

Inherited mutations of CBS result in reducing its activity by destabilization and aggregation. There is precedent that small molecules which specifically bind to and stabilize CBS could restore mutant CBS activity by acting as a pharmacological chaperone (PC). Therefore, this project aims to screen for small molecules that bind to and stabilize CBS using fragment-based x-ray crystallography screening (XChem). XChem involves crystallizing the CBS protein hundreds to thousands of times and then soaking each crystal with a large library of fragments. Any small fragments that bind to CBS will be identified using x-ray crystallography and used as starting points to develop into larger molecules. We will then triage these potential binders against CBS and its disease mutants to determine if they act as PC molecules rescuing their functionality. The most promising small molecules can then be possible starting points for further preclinical studies in cell lines and animal models. Ultimately our proposal aims to discover small molecules as starting points for a PC therapy for classical homocystinuria. 

I am incredibly honoured and excited that our proposal has been funded by the HCU Network America, as this builds on our previous work on the structural biology of CBS along with our goals to develop novel therapies for rare metabolic disorders. As such this research will leverage our group’s multi-disciplinary experience in biophysics, biochemistry, and structural-based drug screening along with guidance from our clinical contacts in the homocystinuria field.


  • Project title: Identification of Compounds to Rescue MMACHC Functional Deficiency in CBLC Disease
  • Principal Investigator: Silvia Vilasi, PhD
  • Amount: $USD 40,000
  • Status: Active
CblC Onlus, HCU Network America and the Organic Acidemia Association have awarded funding to a research project to identify potential treatment for cobalamin C (cblC) deficidency. The reasearch, entitled Identification of Compounds to Rescue MMACHC Functional Deficiency in cblC Disease, will be carried out by Dr. Silvia Vilasi at Institute of Biophysics (IBF) in the National Research Council in Palermo, Italy.

According to the principal investigator, Dr. Silvia Vilasi, the project aims to characterize and classify some of the most common cblC variants of MMACHC protein based on the impact that specific mutation has on MMACHC molecular features, such as structure, stability, B12 binding properties and function. Based on this classification, MMACHC-specific molecules with potential therapeutic benefit and safety will be screened exploiting a structure-based bioinformation approach. The idea is to find molecules able to bind the mutants and stabilize these protein variants in a conformation similar to the unmutated protein (wild type), recovering their function. The protein druggable sites will be targeted with several virtual libraries of drug-like molecules, giving priority to DrugBank library that includes EMA and FDA-approved molecules. 5-10 compounds from the bioinformatic experiments will be then experimentally validated, assessing their ability to restore functionality of proteins. The selected molecules could be precursors for further preclinical studies. Dr. Silvia Vilasi says “I am very happy and honoured to have the possibility to contribute to homocystinuria research and I am grateful to CblC Onlus, HCU Network America and the Organic Acidemia Association for the trust they have placed in the project. The team I will coordinate with at IBF can leverage a wealth of facilities, multidisciplinary skills and backgrounds of the members participating in the project, from experimental biophysics, chemistry, cell biology, structural biology and structure-based drug screening. Moreover, to achieve the proposed goals we will collaborate with Prof. Carlo Dionisi Vici, Head of Clinical and Research Unit of Metabolic Diseases at the Ospedale Pediatrico Bambino Gesù in Rome, who will have an important role in mentoring and guiding the experimental activities as the project is designed to be ‘patient-centered’.”.

Rossella Brindisi, President of CblC Onlus says, “It is a great pleasure to collaborate with HCU Network America and Organic Acidemia Association on this project. It is a good example of cooperation among different organizations spread out in different countries to support scientific research and family community. We hope it will pave the way for further common initiatives.”

President of HCU Network America, Margie McGlynn says, “While HCU Network America’s prior grants were awarded for research projects for potential new therapies for classical homocystinuria, we are pleased to collaborate with cblC Onlus and the Organic Acidemia Association to support a grant focused on potential new therapies for cobalamin C disorder, which is consistent with the expanded focus of HCU Network America. We also hope this project will generate insights that can be applied in the future to other cobalamin disorders.”

Organic Acidemia Executive Director, Kathy Stagni says, “The Organic Acidemia Association is happy to collaborate with HCU America and CblC Onlus on this grant request. We feel fortunate and hopeful that researchers work toward the goal of better treatments for our cobalamin C families.” You can read the press release here


Silvi Vilasi, PhD                Institute of Biophysics in the  National Research Council


  Throughout her career, starting from a hard science such as Physics, (Master Degree in Physics in 2002, at the University of Naples “Federico II”, Naples, Italy), Silvia Vilasi has focused on Life Sciences and human health. Since her PhD thesis (PhD in “Fundamental and applied Physics” in 2006, Biophysics specialization at Perugia University), she has studied the mechanisms (due to mutations or environment), by which a protein folds incorrectly and reaches non- functional conformations and aggregates, causing severe neurodegenerative diseases. She has thus acquired significant expertise in a wide variety of biophysical tools, from microscopic techniques (e.g. atomic force microscopy) to spectroscopy (fluorescence, absorption and circular dichroism) and light scattering on which she continued getting experience during several postdoc fellows (2005-2009, Department of Biochemistry and Biophysics, Second University of Naples, Italy; 2009-2011, Department of Pharmaceutical Sciences, Salerno University, Italy; 2011-2012 Biophysics Institute (IBF), National Research Council (CNR), Italy). From 2012 to 2015 she was a fixed term researcher at IBF-CNR. The position was self-financed since she led one of the research units of the FIRB MIUR project “MIND: Multidisciplinary Investigations for the development of Neuroprotective Drugs” (awarded 845.090 euros), focused on the identification of chemical compounds or molecular chaperones able to counteract the pathological consequences of protein misfolding. The participation to Third International Patient Expert Homocystenurias Meeting in 2019 (Roma, Italy) fueled her involvement with cblC victims and she started working on proteins resulting from cblC mutations, investigating the effect of mutation c.394C>T on MMACHC structure and properties, as evidenced by a recent publication in “Biochimica and Biophysica Acta, Proteins and Proteomics” (https://doi.org/10.1016/j.bbapap.2022.140793).
  • Project title: Evaluation of benefits of thiol-based reductants in classical homocystinuria
  • Principal Investigator: Tomas Majtan, PhD
  • Amount: $USD 40,000
  • Status: Active


The HCU Networks have awarded funding to a research project to evaluate benefits of thiol-based reductants in classical homocystinuria (HCU). The research, entitled Evaluation of benefits of thiol-based reductants in classical homocystinuria, will be carried out by Assistant Research Professor Tomas Majtan at the University of Colorado Anschutz Medical Campus, Aurora.

According to the principal investigator, Tomas Majtan, this project aims to explore whether existing FDA-approved compounds that are thiol-based reductants may prevent binding of homocysteine to cysteine and cysteine residues, which could lead to increased cysteine retention and better elimination of homocysteine from the bloodstream. In addition, anticipated increased availability of homocysteine in plasma could further improve the efficacy of enzyme therapies for homocystinuria that are in development. Tomas Majtan said “The research grant from HCU Network America and HCU Network Australia will allow us to better understand the balance between different forms of homocysteine and how it could be exploited towards better management of CBS-deficient homocystinuria. We are very grateful for this support as we continue our work on expanding therapeutic options for this devastating disease.”

Founder and director of the HCU Network Australia, Tara Morrison said “It was pleasing to receive an increased response to our second call for Expressions of Interest in our 2019 global grants round. We are delighted to announce the recipient of this round, Dr Majtan, and we look forward to his research efforts contributing further to the field. Moreover, we are hopeful this work can lead to the development of a treatment approach that could potentially reduce the need for a protein-restricted diet, which could ease the burden on the affected individual and the people who care for them”.

President of HCU Network America, Margie McGlynn said “We are pleased to provide a grant through the second round of our global grants process to explore this potential new mechanism. Dr. Majtan has been very involved in research on other therapies to address HCU, including a pharmacological chaperone therapy and, more importantly, a potential enzyme replacement therapy, OT-58, under the leadership of his postdoctoral mentor, Jan Kraus. Jan, unfortunately, lost his life to lung cancer in July 2019, and would be so proud to see Tomas being awarded this grant”.

The HCU Networks plan to continue this grant program though issuing calls for Expressions of Interest on a periodic basis. The next call will be announced by fourth quarter of 2020.

You can read the Press Release here
Tomas Majtan  Thomas Majtan, PhD
University of Colorado Anschutz Medical Campus, Aurora

Tomas Majtan received his PharmD in 2003 from the Faculty of Pharmacy, Comenius University in Bratislava studying novel antimicrobial compounds and disinfectants using Salmonella pathogens. He then pursued postgraduate training in microbiology at Slovak Medical University and in 2006 he received a PhD in molecular biology working at the Institute of Molecular Biology of the Slovak Academy of Sciences. During this period, he studied epidemiology and genetics of Salmonella virulence factors and antibiotic resistance markers and deciphered gene expression of bacteriophage during infection of an important industrial strain producing amino acid lysine. In 2007, he started postdoctoral training on enzymology and biochemistry of cystathionine beta-synthase (CBS) in Professor Jan Kraus group at the University of Colorado School of Medicine, Aurora, Colorado. In 2013, he was promoted to Assistant Research Professor at the Department of Pediatrics, Section of Genetics and Metabolism, University of Colorado School of Medicine and continues working on understanding molecular mechanisms behind inborn errors of metabolism and developing new treatments with a focus on homocystinuria.

His contributions to the field include uncovering the mechanism of how missense pathogenic mutations impair CBS function, understanding how CBS cofactors work and affect folding and stability of the WT and mutant enzyme, solving several crystal structures of full-length human CBS to gain structural insight into homocystinuria or clarifying the role of CBS as hydrogen sulfide producing enzyme in health and disease. He utilized his intimate knowledge about CBS and has been working with the late Professor Jan Kraus and Orphan Technologies on enzyme replacement therapy for homocystinuria since 2010.

Dr. Majtan has been a mentor and supervisor of several graduate and postgraduate students or research associates. He is an author of over 40 peer-reviewed papers published in international journals as well as several patents, book chapters and monographs. He regularly presents his research on various conferences and meetings. In addition, he serves as a reviewer for multiple scientific journals and several funding agencies.
  • Project title: New Metabolic strategies for improving treatment of homocystinuria due to CBS deficiency and remethylation defects
  • Principal Investigator: Kenneth N. Maclean, PhD
  • Amount: $USD 40,000
  • Status: Active
The HCU Networks have awarded funding to a research project to investigate the potential usage of metabolic compounds to treat CBS deficient homocystinuria (HCU). The research, entitled New Metabolic strategies for improving treatment of homocystinuria due to CBS deficiency and remethylation defects, will be carried out by Professor Kenneth N. Maclean at the University of Colorado School of Medicine, Denver.


According to principal investigator, Kenneth Maclean, “ A number of lines of evidence have led us to hypothesize that improving our understanding of the regulation of the betaine metabolic pathway in HCU may hold the key to improving treatment in all forms of homocystinuria with a view towards reducing dependence upon methionine restriction and improving clinical outcome”, said Dr. Maclean. “Preliminary work in our laboratory using an animal model of HCU has indicated that this approach has the potential to deliver near normal levels of homocysteine in the presence of a normal protein diet which would represent a highly significant advance in treatment for this condition”. A lot more work is required to capitalize upon these promising early findings and the grant from HCU Network America and HCU Network Australia constitutes an essential first step in that process.”

Founder and director of the HCU Network Australia, Tara Morrison said “the Network is excited to be providing support to this research project which offers the potential to develop a new treatment for the disorder. A treatment approach that could potentially relax or remove the need for a protein-restricted diet is much-needed in this community and would ease the burden on the affected individual and the people who care for them”.

President of HCU Network America, Margie McGlynn said: “It is exciting to award our first grant and to explore this potential new mechanism, and we look forward to expanding our grants program to help improve the diagnosis and treatment of this challenging disease”.

You can read the Press Release here.

Kenneth N. Maclean, PhD

Kenneth N. Maclean, PhD, Professor of Pediatrics, Ehst-Hummel-Kaufman Family Endowed Chair in Inherited Metabolic Disease, Department of Pediatrics, University of Colorado School of Medicine, Denver.


Professor Maclean did his undergraduate degree and PhD in genetics and biochemistry at the University of Greenwich in the United Kingdom. This was followed by a research fellowship at the Hungarian academy of Sciences in Szeged and a post-doc at the Royal London Hospital. Since coming to America in 1997, he has worked primarily on investigating the pathogenic mechanisms involved in cystathionine beta-synthase deficient homocystinuria with a view towards the rational design of novel treatment strategies for this condition.