This year, we celebrate a remarkable milestone for the Department of Human Genetics (DOHG)—our 25th anniversary. This milestone offers a moment of reflection on our journey, from our beginnings as the smallest basic science entity within the School of Medicine to becoming one of Emory's largest basic science departments. Our department's unique combination of basic science and clinical service has advanced basic research and catalyzed novel therapeutic breakthroughs, making a substantial impact on clinical care.

For Women’s History Month (March), Jimena Andersen and Rossana Sanchez Russo are both featured as “Rising Stars” by the School of Medicine.

The School of Medicine’s Diversity and Inclusion week is scheduled for May 20-24, with the theme: From Being to Belonging. Program and registration here.

A review of the Emory campus events held for Black History Month can be found here

Victor Corces

Victor Corces is an underwater photography enthusiast. His favorite places to dive are Indonesia and the Philippines. The dark background is achieved by closing the aperture of the camera to ensure only selected objects are illuminated by the flash. He also uses an “optical snoot”, which he likens to an intense and narrow-beamed flashlight.

Corces came to Emory from Johns Hopkins in 2007. He was born in a small town in the Spanish region of Asturias and studied biochemistry in Madrid. You can read more about his background in this profile.

The Corces lab is interested in understanding how environmental effects on the epigenome interact with individuals’ genome sequence variations to elicit specific phenotypes. They address this broad question in the context of several different biological problems, ranging from autism spectrum disorder (ASD) and ALS/FTD to obesity.

Using brain organoids, investigators in his lab have been probing chemical exposure as partial contributing factors to ASD. They have also established mouse models of trans-generational BPA exposure, and are analyzing post-mortem human brains of individuals with ALS and FTD.

Marcy Schneider

I am an administrative assistant for the Newborn Screening Follow-up Program. I have loved being part of the team helping to save Georgia babies for over 18 years. I have educated many staff members at physicians’ offices by helping them understand the process. My attention to detail has contributed to excellent and accurate follow-up and the success of our program.

Education: B.S. Business Administration, The Ohio State University

What I do for fun:

I enjoy traveling, going to the theater, playing Mahjong, and most importantly spending time with my husband, children and grandchildren. I have received several awards and honors for my community volunteer work.

Maggie Tish

I received a B.S. in neuroscience from the University of Pittsburgh in 2017. Afterwards, I attended the University of Iowa and received a PhD in neuroscience in August of 2023. At Iowa, I worked in the lab of Dr. Joel Geerling in the Neurology department. I studied the neural control of micturition, with particular interest in how this is impaired in normal pressure hydrocephalus, leading to urinary incontinence. My research included designing and characterizing a mouse model of normal pressure hydrocephalus, pathway tracing and identification of neurons projecting to Barrington's nucleus, and the behavioral effects of cell type specific ablation and activation of those neurons.

Acta Neuropathologica, February 3, 2024

Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains

Congratulations to Zachary McEachin, PhD on his first co-senior authored publication as a faculty member, defining a signature of aberrant RNA splicing for a protein pathology. The first author was research specialist Mingee “Tony” Chung, with co-seniors Allan Levey and Nick Seyfried from Neurology/Biochemistry.

A pair of recent studies suggested that cryptic exons are translated to produce peptides that can be detected in cerebrospinal fluid, providing a clinically accessible biomarker for TDP-43 pathology. McEachin and colleagues show which peptides to look for.

Some acronym uncoding: LATE-NC (Limbic-predominant Age-related TDP-43 Encephalopathy neuropathologic changes) is the most common subtype of pathologic TDP-43 protein aggregates. It was first observed in frontotemporal dementia and ALS, and also been observed in Alzheimer’s and Lewy body dementia.

Cell Reports, March 1, 2024

From Steven Sloan, MD, PhD

Neural and metabolic dysregulation in PMM2-deficient human in vitro neural models

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a rare inborn error of metabolism caused by deficiency of the PMM2 enzyme, which leads to impaired protein glycosylation. It is considered the most prevalent CDG, with over 900 reported variants. Neurological symptoms, including developmental delay, are reported in most affected individuals.

Using PMM-deficient 3D human cortical organoids, the authors analyze impaired glycosylation, altered mitochondrial structure and abnormal glucose metabolism. The findings highlight potential limitations for emerging therapies (aldol reductase inhibitors, currently in clinical trials).

Neurobiology of Stress, February 2, 2024

From David Weinshenker, PhD

Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice

In this paper, the Weinshenker lab demonstrated the critical roles of norepinephrine and dopamine in mouse behavioral responses to predator odor.

A few highlights: within the first 10 min of predator odor exposure, dopamine beta-hydroxylase (Dbh)-negative mice displayed high levels of grooming, while controls exhibited robust defensive burying behavior. Dbh-negative mice often fell asleep in shredded bobcat urine-soaked material, whose odor would cause wild type mice to stress out. The findings have implications for understanding anxiety/PTSD as well as Toxoplasma gondii infection, which is known to alter responses to predator odor in a similar way and may alter dopamine metabolism in the host.

Movement Disorders, February 3, 2024

From Hyder Jinnah, MD, PhD

An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm

Jinnah was principal investigator for this Phase II feasibility study of dipraglurant, a negative allosteric modulator of mGluR5 (ahem, fragile X folks). All patients were seen at Emory. The drug was well-tolerated but the 15-participant study showed “no obvious impact on any of the measurement outcomes.” It did allow refinement of study design for future trials on this condition.

Sponsor Addex Therapeutics was developing dipraglurant for Parkinson’s disease with levodopa-induced dyskinesia. A larger PD-LID trial was terminated in 2022, because of pandemic-related recruitment troubles. Now the Swiss company has pivoted and is planning clinical trials for dipraglurant in post-stroke sensorimotor recovery.

eClinicalMedicine, January 12, 2024

From Rossana Sanchez Russo, MD

Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial

For more about this RCT at the patient and family experience level, see the Emory News Story. Sanchez Russo was first author on this paper, along with Gregory Enns of Stanford and investigators in seven countries: United States, United Kingdom, Canada, Austria, France, Germany, Italy. 32 patients enrolled, strong effects on plasma arginine but smaller effects on neurological/mobility symptoms, perhaps because of a floor effect and limited timeframe.

Editorial comment from Quinn:

This study illustrates the tension between biomarkers vs patient-centered outcomes, when it comes to clinical trials. The sponsor of the pegzilarginase trial received a 2022 “refuse to file” response from the FDA (it was approved in Europe). Stung, the sponsor sold rights to the enzyme product to another company, which has announced its plan to re-apply to the US FDA with additional clinical data. Industry experts have called the FDA’s apparent rigor in insisting on robust clinical outcomes “ivory tower thinking” that is inappropriate for a rare disease.

Journal of Biological Chemistry, January 12, 2024

From Bing Yao, PhD

The putative RNA helicase DDX1 associates with the nuclear RNA exosome and modulates RNA/DNA hybrids (R-loops)

Since this paper is partly about R-loops, you know that postdoc Yingzi Hou in Bing’s lab will be involved in this collaboration with Anita Corbett’s lab in Biology.

Mutations in genes encoding several subunits of the ubiquitous RNA exosome are associated with neurological disorders impacting the cerebellum — the question is why? In this paper, DDX1 was identified as interacting with the RNA exosome subunit EXOSC3. The interaction appears to be nucleus-specific, but is lost upon induction of DNA damage.

Journal of Rare Diseases, January 4, 2024

From Dawn Laney and Jingjing Yang, PhD

FDrisk: development of a validated risk assessment tool for Fabry disease utilizing electronic health record data

Dawn Laney founded ThinkGenetic a decade ago, and this is an example of what the company wants to do for Fabry disease. Data were collected retrospectively from deidentified Fabry patients seen at Emory’s Lysosomal Storage Disease Center. Negative controls came from the Fabry Disease Diagnostic Testing and Education project database. Clinical features included demographic information, medical history, patient-reported symptoms and simple tests (such as proteinuria). The model was able to identify patients with risk scores above 50% who should be sent for additional diagnostic testing, with results for males showing higher specificity and positive predictive value.

Cell Reports, January 6, 2024

TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk

TDP-43 is one of those notorious aggregation-prone proteins familiar to researchers studying neurodegenerative diseases. It’s like amyloid and tau, but perhaps not as famous. TDP-43’s cytoplasmic aggregates are considered “the pathological hallmark” of ALS, and its aggregates also can be found in Alzheimer’s brain samples. For more, see the January 2024 Emory News story.

Bing says: “Our results not only provide a common mechanism underlying genome-wide DNA modification dysregulation in several neurodegenerative disorders involved in TDP-43 proteinopathies but also point to a general genomic role of RNA-binding proteins in normal brain functions and diseases.”

American Journal of Case Reports, November 22, 2023

From Jaime Vengoechea Barrios, MD and co-authors from Renal Division

Autosomal Recessive Adolescent Syndromic Nephronophthisis Caused by a Novel Compound Heterozygous Pathogenic Variant

19-year-old woman with two pathogenic variants in NPHP3 (encodes ciliary protein, part of Wnt pathway), resulting in nephronophthisis: advanced kidney and liver disease. The patient is “currently listed for simultaneous liver/kidney transplant.”

American Journal of Medical Genetics Part A, November 13, 2023

From Rana Al-Jaberi, MD and Jaime Vengoechea Barrios, MD

Isolated cardiomyopathy in a pathogenic X-linked in frame hemizygous DMD exon 49 deletion: A rare presentation with normal creatine kinase levels and absence of musculoskeletal symptoms

Case report describes a patient, previously a healthy marathon runner, who came to the hospital with acute heart failure and atrial fibrillation. His LV ejection fraction was 14% (very low). In the hospital, he had IV diuresis and medical therapy (amiodarone, milrinone and metoprolol), underwent cardioversion and later had a cardiac ablation to resolve atrial fibrillation. His ejection fraction was restored, and he was back engaging in aerobic exercise and weightlifting three times per week.

Our medical geneticists first used a 92-gene cardiomyopathy/arrhythmia panel, and then DMD-specific testing through exon arrays from GeneDx, to find that the patient had a pathogenic deletion in DMD exon 49. Deletions in exon 49 mostly result in a mild Becker muscular dystrophy phenotype.