July 31, 2023
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Purpose
The purpose of this announcement is to notify the research community that the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is interested in receiving grant applications focused on skin research uncovering the basis for inferior diagnosis, increased prevalence, elevated clinical severity, and altered treatment response in Black Americans and African Americans, Hispanics and Latinos, American Indians and Alaskan Natives, Asians and Asian Americans, and Native Hawaiians and Pacific Islanders with skin diseases.
Background
Existing under studied skin types in biomedical research and ongoing rapid demographic changes in the United States both require better understanding of biological mechanisms and improved prevention and treatment of skin diseases in patients with understudied skin types. Compared to European ancestry populations, Black American and African American, Hispanic and Latinos, American Indian and Alaskan Native, Asian and Asian American, and Native Hawaiian and Pacific Islander populations, experience increased prevalence, elevated severity of clinical features, and altered treatment response in multiple skin diseases. As such, much higher prevalence of hidradenitis suppurativa, atopic dermatitis, acne and vitiligo was described in the populations of African American and Hispanic and Latinos genetic ancestry. Further, increased prevalence of oculocutaneous albinism type 2, keloids and prurigo nodularis is characteristic for African American populations, while cutaneous discoid lupus erythematosus is both significantly more prevalent and more often leads to skin dyspigmentation and scarring alopecia in African Americans. Also, exacerbated clinical course is more often observed in African American patients affected by psoriasis and in Asian, Asian American, Native Hawaiian and Pacific Islander patients experiencing Stevens-Johnson syndrome and toxic epidermolysis necrolysis. Despite this accumulating knowledge and known differences in skin anatomy and physiology among groups that may partly explain disparities in cutaneous disorders based on genetic ancestry, the cellular and molecular mechanisms underpinning higher disease prevalence and severity in the populations remain to be defined. Finally, a difficulty in diagnosis of common conditions such as acne, atopic dermatitis and psoriasis in patients with pigmented skin stems from a paucity of ethnic skin images in core dermatology educational resources and the research setting, often resulting in delays, misdiagnoses, and higher frequency of skin biopsies.
Starting to address this knowledge gap, a recent global transcriptome analysis of healthy African American skin revealed 570 differentially expressed genes, with only four among them being related to melanogenesis and skin pigmentation. The identified set included genes encoding proinflammatory cytokines such as TNF-alpha and IL-32; Igs and their receptors such as FCER1G; as well as epidermal differentiation complex and keratins. Of note, enrichment of the components of IL-13 and IL-4 signaling pathways in healthy African American skin overlapped with the molecular signature of atopic dermatitis. Moreover, a greater dermal infiltration of dendritic cells bearing high affinity IgE receptor FCER1, higher serum IgE levels, increased Th2 and Th22 induction, and upregulation of Th17 axis in the skin were all observed in the initial studies of African American patients with atopic dermatitis, indicating that aggravated course of the disease may be associated with a broader immune activation. Finally, statistically significant variation in the levels of systemic inflammation markers such as C-reactive protein, ferritin, and eosinophils was found in African American patients with prurigo nodularis. Larger subsequent studies utilizing ancestry informative markers should allow for appropriate analyses of more admixed populations and provide rationale for stratified clinical trials based on genetic ancestry. In turn, this approach may help to determine how distinct molecular phenotypes in patients with under studied skin types translate into differential clinical course and treatment strategies for skin diseases.
Currently, some genetic ancestry populations are significantly underrepresented in genome sequencing projects as the percentages of individuals included in genome-wide association studies (GWAS) based on genetic ancestry are 78% European, 10% Asian, 2% African, 1% Hispanic, whereas all others represent less than 1%. While the patterns of genetic variation can affect both disease risk and treatment efficacy and safety, a majority of studies still occur in European ancestry populations, thus limiting the utility of the results across a variety of human populations. Crucially, this bias effectively translates into poorer disease prediction and treatment for individuals of under-represented genetic ancestries. Importantly, studying diverse populations increases our ability to broadly understand genetic disease architectures that will ultimately lead to increased precision in medical care. Likewise, the Black American and African American, Hispanic and Latinos, American Indian and Alsakan Native, Asian and Asian American, and Native Hawaiian and Pacific Islander populations are grossly underrepresented in basic, translational, and clinical NIAMS-funded studies focusing on the skin. This fundamental research gap has created a significant unmet need for better prevention and improved therapeutic approaches in under studied skin types.
Research Objectives
This NOSI invites administrative supplements to active grants that expand the original research goals with a new focus on improving the understanding of skin diseases and conditions within the NIAMS mission in patients with under studied skin types. The generated knowledge should yield basic, translational, and clinical insights to improve health pertinent to disorders of skin and specifically benefit Black Americans and African Americans, Hispanics and Latinos, American Indians and Alaskan Natives, Asians and Asian Americans, and Native Hawaiians and Pacific Islanders as populations with under-studied skin types. It may also gather evidence towards a future innovative study or new scientific direction to accelerate research in these under studied skin types.
Examples of research topics include, but are not limited to:
Other considerations:
Application and Submission Information
This notice applies to due dates on or after October 5, 2023 and subsequent receipt dates through July 16, 2026.
Submit applications for this initiative using one of the following (NOFOs) or any reissues of these announcements through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following additions:
Although NIAMS is not listed as a Participating Organization in all the NOFOs listed above, applications for this initiative will be accepted.
Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.
Although NIAMS is not listed as a Participating Organization in all the NOFOs listed above, applications for this initiative will be accepted.
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.
Scientific/Research Contact(s)
Skin Biology and Diseases Group:
Alexey Belkin, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 240-755-3031
Email: [email protected]
Ricardo Cibotti, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-792-4871
Email: [email protected]
Peer Review Contact(s)
Kathy Salaita, Sc.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5033
Email: [email protected]
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Financial/Grants Management Contact(s)
Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-7760
Email: [email protected]