Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Otorhinolaryngology-Head & Neck Surgery
Secondary Appointment(s):
BioChemistry&Molecular Biology, Ophthalmology
Administrative Title:
Co-Director for Academic Development
Additional Title:
Professor
Location:
HSF3, 670 West Baltimore St, Room 7120
Phone (Primary):
410-706-3799
Phone (Secondary):
410-7063094
Education and Training
B.Sc. 1995 Medical Laboratory Technology, University of the Punjab, Lahore, Pakistan.
M.Sc. 1998 Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Ph.D. 2002 Molecular Genetics, National Centre for Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan.
Biosketch
Dr. Ahmed received his Bachelor and PhD degrees from the University of Punjab, Pakistan. He accomplished his pre-doctoral as well as his post-doctoral trainings at the National Institute for Deafness and Communication Disorders, NIDCD/NIH. In 2009 he joined the Cincinnati Children’s Hospital Medical Center, and University of Cincinnati, Cincinnati, Ohio as an Assistant Professor of Ophthalmology, Otolaryngology and Human Genetics. He was subsequently promoted to Associate Professor with tenure in 2013. In July 2014, Dr. Ahmed joined the University of Maryland as an Associate Professor of Otorhinolaryngology, Ophthalmology and Biochemistry. In July 2016, Dr. Ahmed was promoted to Professor rank. Dr Ahmed’s scientific accomplishments have earned several national and international awards, including Career Development Award by the RPB Foundation and a Medal of Honor by the President of Pakistan. He has been continuously funded as a principal investigator since 2007.
Dr. Ahmed long-term goal is to understand how the retinal and inner ear sensory epithelia develop and function. His lab study inherited human disorders of retina and inner ear, like Usher syndrome (USH) and Oculocutaneous Albinism (OCA) to improve our understanding of these organs at the molecular level, to study the pathophysiology of these disorders in animal models for the purpose of developing new strategies to prevent and treat these neurosensory disorders. The studies under investigation are designed to answer the following broad questions: What are the precise mechanisms of various forms of hearing and vision dysfunction? What are the genetic factors that determine light sensitivity? How do the pathogenic mutations in disease-causing genes affect the ear, eye and skin structure and function? And which molecules or genetic factors can exacerbate and/or mitigate the effects of disease-causing genes? For these studies, families segregating inherited USH and OCA are being collected. Mutant mouse and zebrafish models have been developed and his lab evaluates them to understand the function of new proteins. Functional analysis of the newly identified genes associated with deaf-blindness and OCA promises new insights into the molecular mechanisms of vision and auditory development and functions and will facilitate the rational design of potential therapies.
Research/Clinical Keywords
Genetic disorders of Ear and Eye, hearing loss, Usher syndrome, Retinitis pigmentosa, hearing restoration, gene therapy, Otitis media genetics, Inner ear development, Mechanotransduction, Calcium role in hearing and vision, Noise induced hearing loss, Genome editing
Highlighted Publications
Yousaf S, Sethna S, Chaudhary MA, Shaikh RS, Riazuddin S, Ahmed ZM. Molecular characterization of SLC24A5 variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6. Pigment Cell Melanoma Res. 2020; 33(4):556-565.
Sheikh SA, Sisk RA, Schiavon CR, Waryah YM, Usmani MA, Steel DH, Sayer JA, Narsani AK, Hufnagel RB, Riazuddin S, Kahn R, Waryah AM, Ahmed ZM. Homozygous variant in ARL3 causes autosomal recessive cone dystrophy. IOVS, 2019; 60(14):4811-4819.
Schrauwen I, Giese APJ, Aziz A, Lafont DT, Chakchouk I, Santos-Cortez RLP, Lee K, Acharya A, UWCMG, Nickerson DA, Bamshad MJ, Ali G, Riazuddin S, Ansar M, Ahmad W, Ahmed ZM, Leal SM. FAM92 underlies non-syndromic postaxial polydactyly in humans and an abnormal limb and digit skeletal phenotype in mice. J Bone and Mineral Res. 2019; 34(2):375-386.
Ahmed ZM, Jaworek TJ, Sarangdhar GN, Zheng L, Gul K, Khan SN, Friedman TB, Sisk RA, Bartles JR, Riazuddin Sh, Riazuddin S. In-frame deletion of human ESPN is associated with deafness, vestibulopathy and vision impairment. J Med Genet. 2018 Jul; 55(7):479-488.
Giese APJ, Tang YQ, Sinha GP, Bowl MR, Goldring AC, Parker A, Freeman MJ, Brown SDM, Riazuddin S, Fettiplace R, Schafer WR, Frolenkov GI, Ahmed ZM. CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells. Nat Comm. 2017 8:43.
Shahzad M. Yousaf S, Waryah YM, Gul H, Kausar T, Tariq N, Mahmood U, Ali M, Khan MA, Waryah AM, Shaikh RS, Riazuddin S, Ahmed ZM, UWCMG. Molecular outcomes, clinical consequences, and genetic diagnosis of Oculocutaneous Albinism in Pakistani population. Sci Reports. 2017 Mar 7; 7:44185.
Riazuddin S, Hussain M, Razzaq A, Iqbak Z, Shahzad M, Polla DL, Song Y, van Beusekom K, Khan AA, Tomas-Roca L, Rashid M, Zahoor MY, Wissink-Lindhout WM, Basra MAR, Ansar M, Agha Z, van Heeswijk K, Rasheed F, M Van de Vorst, Veltman JA, Gilissen C, Akram J, Kleefstra T, Assir MZ, UK10K, Grozeva D, Carss K, Raymond HL, O’Connor TD, Riazuddin SA, Khan SN, Ahmed ZM, de Brouwer APM, van Bokhoven H, Riazuddin S. Exome sequencing of Pakistani Consanguineous Families identifies 30 novel candidate genes for recessive Intellectual Disability. Mol Psychiatry. [Epub ahed of print].
Waryah AM, Shahzad M, Shaikh H, Sheikh SA, Channa NA, Hufnagel RB, Makhdoom A, Riazuddin S, Ahmed ZM. A novel CHST3 allele associated with Spondyloepiphyseal dysplasia and hearing loss in Pakistani kindred. Clin Genet, 2016; 90:90-95.
Fong KSK, Hufnagel RB, Khadka V, Corley MJ, Maunakea AK, Fogelgren B, Ahmed ZM, Lozanoff S. A mutation disrupting TET1 activity alters the expression of genes critical for neural tube closure in the tuft mouse. Dis Model Mech. 2016; 9:585-596.
Shahzad M, Campos JS, Tariq N, Serrano CH, Yousaf R, Jiménez-Cervantes C, Yousaf S, Waryah YM, Dad HA, Blue EM, Sobreira N, López-Giráldez F, UWCMG, Kausar T, Ali M, Waryah AM, Riazuddin S, Shaikh RS, García-Borrón JC, Ahmed ZM*. Identification and functional characterization of natural human melanocortin 1 receptor (MC1R) mutant alleles in Pakistani population. Pigment Cell Melanoma Res. 2015; 28:730-735.
Santos-Cortez RLP, Chiong CM, Reyes-Quintos MRT, Tantoco MLC, Wang X, Acharya A, Abbe I, Giese AP, Allen EK, Smith JD, Li B, Paz EMCL, Garcia MC,Llanes EGDV, Labra PJ, Gloria-Cruz TLI, Chan AL, Wang GT, Daly KA, UWCMG, Shendure J, Bamshad MJ, Nickerson DA, Patel JA, Riazuddin S, Sale MM, Chonmaitree T, Ahmed ZM, Abes GT, Leal SM. Rare A2ML1 variants confer susceptibility to Otitis Media. Nat Genet. 2015; 47(8):917-920.
Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schule R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Nemeth AH, Carelli V, Huang T, Zuchner S, Dallman JE. Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder. Nat Genet. 2015; 47(8):926-932.
Shaikh RS, Reuter P, Sisk RA, Kausar T, Shahzad M, Maqsood MI, Yousif A, Ali M, Riazuddin S, Wissinger B, Ahmed ZM. Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy. Eur J Hum Genet. 2015; 23(4):473-480.
Ahmed ZM, Frolenkov GI, Riazuddin S. Usher proteins in inner ear structure and function. Physiol Genomics. 2013; Nov 1;45(21):987-9.
Riazuddin S, Belyantseva I, Giese A, Lee K, Indzhykulian AA, Nandamuri SP, Yousaf R, Sinha GP, Lee S, Terrell D, Hegde RS, Ali RA, Anwar S, Andrade-Elizondo PB, Sirmaci A, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Ahmad W, Khan SN, Akram J, Tekin M, Riazuddin S, Cook T, Buschbeck EK, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZM. Alterations of the CIB2 calcium and integrin binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet. 2012; 44(11):1265-1271. (featured in Editor’s Choice of Science).
Ahmed ZM, Yousaf R, Lee BC, Khan SN, Lee S, Lee K, Husnain T, Rehman AU, Bonneux, S, Ansar M, Ahmad W, Leal SM, Gladyshev VN, Belyantseva IA, Van Camp G, Riazuddin S, Friedman TB, Riazuddin S. Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are associated with human deafness DFNB74. Am J Hum Genet. 2011; 88(1):19-29.
Kitajiri SI, Sakamoto T, Belyantseva IA, Goodyear RJ, Stepanyan R, Fujiwara I, Bird JE, Riazuddin S, Riazuddin S, Ahmed ZM,Hinshaw JE, Sellers J, Bartles JR, Hammer JA, Richardson GP, Griffith AJ, Frolenkov GI, Friedman TB. Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing. Cell. 2010; 141:786-798.
Ahmed ZM, Riazuddin S, Aye S, Ali RA, Venselaar H, Anwar S, Belyantseva PP, Qasim M, Riazuddin S, Friedman TB. Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndrome. Hum Genet. 2008; 124(3):215-223.
Ahmed ZM, Masmoudi S, Kalay E, Belyantseva IA, Mosrati MA, Collin RWJ, Riazuddin S, Hmani-Aifa M, Venselaar H, Kawar MN, Abdelaziz T, Zwaag BVD, Khan SY, Ayadi L, Riazuddin SA, Morell RJ, Griffith AJ, Charfedine I, Çaylan R, Oostrik J, Karaguzel A, Ghorbel A, Riazuddin S, Friedman TB, Ayadi H, Kremer H. Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans. Nat Genet. 2008; 40(11):1335-1340.
Riazuddin S, Ahmed ZM, Fanning AS, Lagziel A, Kitajiri S, Ramzan K, Khan SN, Chattaraj P, Friedman PL, Anderson JM, Belyantseva IA, Forge A, Riazuddin S, Friedman TB. Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet. 2006; 79(6):1040-1051.
Ahmed ZM, Goodyear R, Riazuddin S, Lagziel A, Behra M, Burgess SM, Wilcox ER, Riazuddin S, Griffith AJ, Frolenkov G, Belyantseva IA, Richardson G, Friedman TB. The tip link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15. J Neuroscience. 2006; 26:7022-7034.
Belyantseva IA, Boger ET, Naz S, Frolenkov GI, Sellers JR, Ahmed ZM, Griffith AJ, Friedman TB. Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia. Nat Cell Bio. 2005; 7(2):148-156.
Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RJ, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB. A mutation of PCDH15 among Ashkenazi Jews with type I Usher syndrome. N Engl J Med. 2003; 348(17):1664-1670.
Kurima K, Peters LM, Yang Y, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo J, Makishima T, Ghosh M, Menon PSN, Deshmukh D, Oddoux C, Ostrer H, Khan S, Riazuddin S, Deininger PL, Hampton LL, Sullivan SL, Battey JFJr., Keats BJB, Wilcox ER, Friedman TB, Griffith AJ. Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet.2002;30(3):277-284.
Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, Morell RJ, Friedman TB, Riazuddin S, Wilcox ER. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet. 2001; 69(1):25-34.
Riazuddin S, Castelein CM, Ahmed ZM, Lalwani AK, Mastroianni MA, Naz S, Smith TN, Liburd NA, Friedman TB, Griffith AJ, Riazuddin S, Wilcox ER. Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nat Genet. 2000; 26(4):431-434.
Research Interests
Usher syndrome
Restoration of Hearing and Vision loss
Genetics of Hearing and vision inherited disorders
Genetics of acquired hearing loss
Gene therapies
Here are a few examples of ongoing projects in Dr. Ahmed’s lab:
Prevent hearing and vision loss in protocadherin 15 mutant mice
Mutations in PCDH15, encoding protocadherin 15, causing deafness or deaf-blindness syndrome (Usher syndrome) were first reported in 2001. Later on studies provide essentail clues about the spatio-temporal expression profile of PCDH15 in the human and mouse inner ear and retinal tissues and it's role in the development and maintenance of ear and eye functions. A single point mutation, p.R245X, in PCDH15 is responsible for over 60% of Usher syndrome type IF cases in Askenazi Jews. Ahmed's lab is currently investigating various strategies to prevent hearing and vision loss in Pcdh15 mutant mice, with an aim to develop therapeutic interventions for individuals suffering with Usher syndrome type 1F.
Role of Calcium and Integrin binding protein CIB2 in the inner ear and retina
In our recent study, we have identified 57 consanguineous Pakistani families segregating non-syndromic hearing impairment (DFNB48) or Usher syndrome type I (USH1J) linked to the mutations in CIB2, a gene that encodes a calcium binding protein. We have identified at least 3 different mutations in CIB2 that lead to non-syndromic hearing loss and one mutation causing Usher syndrome. To date, these mutations are the most common and prevalent genetic cause of non-syndromic hearing loss in Pakistan. But mutations in CIB2 are not confined to Pakistani population. We have recently identified additional mutations in CIB2 that cause hearing loss in Turkish, Danish and US population. Identification of this new gene means improvement in our genetic diagnostic abilities, genetic counseling and molecular epidemiology of hearing loss.
The reason why we think this particular Usher syndrome might be better suited for future interventions is because of the nature of the protein discovered. All previous mutations associated with Usher syndrome affect the proteins involved in building the structure of the sensory cells. This means that the sensory cells are likely to be malformed or disorganized in an adult organism. Of course, correcting the structural pathology is a very challenging task. In contrast, the mutations of CIB2 that we discovered seem to have much more subtle effects. We speculate that these mutations may affect only the calcium homeostasis in the sensory cells, although more functional studies are needed to test this hypothesis and function of CIB2 in the inner ear and retina. To this end, we have developed several CIB2 mouse lines. We are currently working to characterize the hearing and the visual phenotype of these mice through calcium and electronic microcopy imaging, immunological and physiological studies.
Genetics of Oculocutaneous Albinism: predisposition for Skin Cancer
Our lab is currently studying Oculocutaneous albinism (OCA), which is a form of albinism that involves the eye, skin, and often hair. This recessive disorder is caused by defects in the melanin synthesis pathway. Polymorphisms in some of the pigmentary pathway genes (e.g. TYR, OCA2, TYRP1 and SLC45A2) increase susceptibility for skin cancer, which affects all ages, genders and societies worldwide. Malignant melanoma is the major cause of deaths from skin cancer and a large number of studies revealed that the risk of malignant melanoma correlated with genetic, personal characteristics and a person’s ultraviolet (UV) exposure behavior. We are ascertaining large families segregating OCA phenotype from various populations around the globe. There are many cases of OCA in which the causative gene remains unknown. Therefore, a need clearly exists for further genetic understanding of this disease, as does the opportunity to minimize the cases of preventable skin cancers. We are currently working to identify novel genes involved in these disorders.
Awards and Affiliations
2006 NIH Fellow Award for Research Excellence, National Institutes of Health, Bethesda, MD, USA.
2006 Third World Academy of Science Prize in Biology, Pakistan Science Foundation, Islamabad, Pakistan.
2007 NIH Fellow Award for Research Excellence, National Institutes of Health, Bethesda, MD, USA.
2008 Medal of Honor (Tamgha-i-Imtiaz) from the President of Pakistan, Government of Pakistan, Islamabad, Pakistan.
2010 Career Development Award, Research to Prevent Blindness Foundation, USA.
2018 O’Brien Trust Award, Deborah Munroe Noonan Memorial Research.
2015 - pres Adjunct Professor of Biochemistry & Molecular Biology, Faculty of Science & Technology, GC University, Faisalabad, Pakistan.
2016 - pres Adjunct Faculty, Neuroscience and Cognitive Science (NACS) program, University of Maryland, College Park, MD, USA.
2016 – pres Associate Member, Molecular and Structural Biology Program in Oncology, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center.
2016 - pres Professor, Tenure Track, Department of Otorhinolaryngology Head & Neck Surgery, University of Maryland School of Medicine
2016 – pres Professor (secondary appointment), Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine
2016 – pres Professor (secondary appointment), Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine
Grants and Contracts
12/01/2012 - 11/30/2022
"Usher proteins in the inner ear structure and function"
NIH R01, DC012564-01
Role: PI
05/15/2018 - 04/31/2023
"Molecular Determinants of Usher syndrome in humans"
NIH R01, DC016295-01A1
Role: PI
02/10/2016-01/30/2021
"Otitis Media susceptibility and middle ear microbial shifts due to gene variants"
NIH R01, DC015004-01
Role: Co-I
07/01/2017-06/30/2022
"Identification of Autosomal Recessive Nonsyndromic Hearing Impairment Genes"
NIH R01, DC0003594
Role: Co-I
07/01/2020-06/30/2023
"Identification of Nonsyndromic Hearing Impairment Genes in Sub-Saharan Africa"
NIH R01, DC016593
Role: Co-I
07/01/2017 - ongoing
Usher 1F Collaborative Research Funds
Community Service
2017 – 2020 President, Board of Director Atwood and Timberline Lane at Turf Valley, Home Owner Association, Inc.
2017 – 2023 Member, Board of Director Atwood and Timberline Lane at Turf Valley, Home Owner Association, Inc.
Patents
- Modulation of mTORC1 Activity and Autophagy via CIB2-RHEB Interaction. PCT/US2019/044745 (pending approval)