Harvard Catalyst Profiles

Contact, publication, and social network information about Harvard faculty and fellows.

Harvard Catalyst Profiles is currently experiencing a partial system outage. Login/Edit modules are currently disabled.

Eric Adam Pierce, M.D., Ph.D.

Title
Institution
Department
Address
Phone
Fax

Overview
Please note that the correct contact information is as follows:
Tel: 617-573-6917
Fax: 617-573-6920
Email: eric_pierce@meei.harvard.edu


Molecular Genetics of Inherited Blindness
Inherited retinal degenerations such as retinitis pigmentosa (RP) are common causes of blindness. The overall goals of our research program are to improve our understanding of the molecular bases of inherited retinal degenerations and related cilia disorders so that rational therapies can be developed for these diseases.

We currently have 4 active research projects directed towards these goals:

1. The Biology and Diseases of Photoreceptor Sensory Cilia
Cilia are present on most cells in the human body. These structures are typically sensory organelles, and are involved in many critical aspects of cell biology and development. The photoreceptor sensory cilium (PSC) elaborated by each rod and cone photoreceptor cell of the retina is a classic example. Consistent with the importance of cilia in biology, mutations in genes that encode cilia components are common causes of disease. Mutations that cause inherited retinal degenerations, which are common causes of blindness, have been identified in genes encoding more than 40 PSC proteins to date. These disorders are characterized by PSC dysfunction, followed by degeneration and death of the photoreceptor cells, resulting in loss of vision.

We are interested in studying how photoreceptor sensory cilia are built and maintained, and how these processes are disrupted in disease. For example, while there has been notable progress identifying the genetic causes of inherited retinal degenerations and other cilia disorders, the genes that harbor mutations which cause disease in half of patients with inherited retinal degeneration remain to be identified. To help understand PSCs better, and facilitate identification of new retinal degeneration disease genes, we performed a series of proteomic analyses to identify all of the proteins in mouse photoreceptor sensory cilia. The results show that PSCs are made of almost 2000 proteins, including ~1500 proteins not detected in cilia from lower organisms. This database of PSC proteins has already proved to be very useful. For example, in the past year we have used the list of genes that encode novel PSC proteins to help identify one confirmed and four potential new retinal degeneration disease genes.

Retinitis Pigmentosa 1
Part of our work on PSCs is focused on the retinitis pigmentosa 1 (RP1) protein. Mutations in RP1 are a common cause of dominant RP, which is the most common form of inherited retinal degeneration. Work in our lab has found that the RP1 protein is a photoreceptor microtubule-associated protein that is required for the correct formation of PSCs. We are now working to identify proteins that interact with RP1 in order to further define how it participates in PSC formation, and study how its mutations lead to photoreceptor cell death. We are also beginning to test potential therapies for RP1 disease, including gene augmentation therapy, in point mutation Rp1 knockin mice.

2. RNA Splicing Factor Retinitis Pigmentosa
Mutations in genes that encode the RNA splicing factors are common causes retinitis pigmentosa (RP). Despite their prevalence, the pathogenesis of these disorders is not understood. The splicing factors affected, pre-mRNA processing factor (PRPF) 3, PRPF6, PRPF8, PRPF31 are highly conserved components of the spliceosome, the complex which excises introns from nascent RNA transcripts to generate mature mRNAs. Since RNA splicing is required in all cells, it is not clear how mutations in these ubiquitous proteins lead to retina-specific disease. We hypothesize that mutations in these RNA splicing factors disrupt RNA splicing and lead to the generation of aberrant transcripts and proteins in the retina and other tissues, one or more of which are pathogenic in the retina. We have generated Prpf3 and Prpf8 knockin mice, and obtained Prpf31 mutant mice from collaborators, to investigate the pathogenesis of the RNA splicing factor forms of RP. We are now using next generation sequencing based transcriptome analyses to identify aberrant mRNAs that may be pathogenic in these disorders.

3. Inherited Macular Degeneration
Age-related macular degeneration (AMD) is one of the most common cause of vision loss in developed countries. The most characteristic clinical finding in the retinas of patients with AMD is drusen, or extracellular deposits of protein, lipid and debris that accumulate underneath the retinal pigment epithelium (RPE). At present, the etiology of drusen in AMD is not known, and there are only limited treatments are available to prevent the progression of AMD. In order to gain insight into the pathogenesis of AMD, we are studying an inherited form of macular degeneration called Doyne honeycomb retinal dystrophy (DHRD)/Malattia Leventinese (ML). Both DHRD and ML are caused by a single mutation, Arg-345 to Trp (R345W), in the EFEMP1 or Fibulin-3 gene. We have used gene targeting techniques to introduce this mutation into the Efemp1 gene of mice. We have found that the Efemp1-R345W knockin mice develop AMD-like deposits under their retinas, and are now using proteomic analyses to study the pathogenesis of these lesions.

4. Oligonucleotide-Directed Gene Targeting and Gene Correction
The fundamental premise of this project that oligodeoxynucleotides (ODNs) can be used to introduce sequence-specific alterations into the genomic DNA of stem cells. In mouse embryonic stem (ES) cells, the goal of ODN-mediated gene targeting is to create knock-in mouse models of human disease. In adult and induced pluripotent stem cells (iPS), the use of ODNs is directed toward the therapeutic correction of pathogenic mutations in human disease genes. Results generated from our research and from other investigators in the past several years have demonstrated proof of principle for this approach. We are workinng to build on these successes to develop strategies for broad application of ODN-mediated gene correction for the treatment of human disease and ODN-mediated gene targeting for the generation of mouse models of disease.

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01EY026904 (PIERCE, ERIC A) Sep 30, 2017 - Jun 30, 2022
    NIH
    Genetic Causes and Genetic Modifiers of Inherited Retinal Degenerations
    Role: Principal Investigator
  2. R01EY020902 (PIERCE, ERIC A) Jul 1, 2010 - Mar 31, 2025
    NIH
    The Pathogenesis of RNA Splicing Factor Associated Retinal Degeneration
    Role: Principal Investigator
  3. R03EY013776 (PIERCE, ERIC A) Aug 1, 2001 - Jul 31, 2003
    NIH
    ANIMALS WITH TARGETED MUTATIONS IN PHOTORECEPTOR GENES
    Role: Principal Investigator
  4. R01EY012910 (PIERCE, ERIC A) Jul 8, 1999 - Jul 31, 2028
    NIH
    Precision Medicine for Inherited Retinal Degenerations
    Role: Principal Investigator
  5. K11EY000343 (PIERCE, ERIC A) Jul 1, 1994 - Jun 30, 1999
    NIH
    BIOCHEMICAL BASIS OF RETINAL NEOVASCULARIZATION
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
Updating...
This operation might take several minutes to complete. Please do not close your browser.
Local representatives can answer questions about the Profiles website or help with editing a profile or issues with profile data. For assistance with this profile: HMS/HSDM faculty should contact contactcatalyst.harvard.edu. For faculty or fellow appointment updates and changes, please ask your appointing department to contact HMS. For fellow personal and demographic information, contact HMS Human Resources at human_resourceshms.harvard.edu. For faculty personal and demographic information, contact HMS Office for Faculty Affairs at facappthms.harvard.edu.
Pierce's Networks
Click the
Explore
buttons for more information and interactive visualizations!
Concepts (517)
Explore
_
Co-Authors (60)
Explore
_
Similar People (60)
Explore
_
Same Department 
Explore
_
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.