Dr. Carmen L. Cadilla

Dr. Carmen L. Cadilla

Contact Info


  • Postdoctoral in Biochemistry and Molecular Biology, 1989
    Oak Ridge National Laboratories-Biology Division
  • Ph.D. in Biomedical Sciences, Major in Biochemistry, 1986, University of Tennessee, Knoxville
    Oak Ridge Graduate School of Biomedical Sciences
  • M.S. in Chemistry, Major in Organic Chemistry, 1980, University of Puerto Rico Rio Piedras Campus
  • B.S. in Chemistry, Summer 1977, University of Puerto Rico Mayagüez Campus

Mechanisms of regulation of gene expression and Molecular genetic and genomic studies in the Puerto Rican population.

Research Interests

Our laboratory focuses on the study of the biological and biochemical mechanisms affected in genetic disorders that affect the Puerto Rican population. We have worked on two rare disorders that are more frequent in our population than in the rest of the world, the Hermansky Pudlak and Setleis Syndromes. We have also applied genomic methodologies to research questions in human disease as well as model organisms. In addition, in collaboration with Dr. Jorge Duconge, Professor of the School of Pharmacy, we also study genetic variants involved in the response to drugs. In collaboration with Dr. Juan Lopez Garriga, Professor of Chemistry at UPR Mayagüez, we have studied the genes that code for hemoglobins of the clam Lucina pectinata and their regulation, as well as site-directed mutagenesis of heme pocket residues involved in ligand recognition, in addition to current work in genomics and transcriptomics of this model organism.

Research interests are focused on:

Structure and function studies of the bHLH proteins of the Twist subfamily. Role of Twist2 in human development.

Identification of genes causing disease or genetic conditions in the Puerto Rican population.

An Example of our work:

PMC full text: Franco HL, Casasnovas J, Rodríguez-Medina JR and Cadilla CL (2011) Redundant or Separate Factors? Roles of Twist1 and Twist2 as molecular switches in gene transcription.

Nucleic Acids Res. 2011 Mar; 39(4): 1177–1186.


Copyright © The Author(s) 2010. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Figure 2.
Modes of transcriptional regulation by Twist1 and Twist2. The Twist1 (TW1) and Twist2 (TW2) bHLH transcription factors exhibit a bifunctional role by acting as activators and repressors depending on post-translational modifications, partner choice and cellular context (6,7,28). (A) The mode of action employed by Twist1 and Twist2 was first understood in genes involved in muscle development. The myogenic bHLH factors such as MyoD bind as heterodimers with E-proteins to E-boxes found in regulatory regions of muscle-specific genes. MyoD-mediated activation typically requires the binding of MEF2 and involves the recruitment of HATs. Twist acts as a repressor by promoting deacetylation either by blocking HAT activity or recruiting HDACs (35,38). (B) The role of Twist during osteogenesis was highlighted when mutations of Twist1 were identified in SCS patients. Based on the SCS mouse model and studies in human osteoblasts, it was determined that Twist1 acted before Twist2 on osteoblast maturation (20,23). Twist1, as a heterodimer with E12, represses the FGFR2 gene, and as Id protein levels rise, E12 gets sequestered leading to Twist1 homodimerization. As a homodimer, Twist1 activates FGFR2 which mediates downstream activation of RunX2 (26,42). Aside of FGF signaling, both Twist1 and Twist2 can block the transactivation activity of the master regulator RunX2 (25). (C) Twist can repress genes independent of DNA binding. For example, Twist can sequester E12 or MyoD leading to the repression genes of the myogenic program. By doing so, Twist mimics the mechanism of inhibition employed by the Id proteins. (D) Twist partner choice can be determined by the phosphorylation state of these proteins leading to homodimerization, or heterodimerization with Class A and Class B bHLH factors. E-box selection can also be influenced by phosphoregulation. In this case, affinity for a class B bHLH factor, Hand2, is favored when Twist1 is phosphorylated by PKA (29,31). (E) The Twist2 KO mouse suggests a role of Twist2 in regulating cytokine gene expression (22). This work lead to a proposed negative feedback loop in which inflammatory cytokines activate NF-kB, and NF-kB activates the expression of cytokines and both Twist1 and Twist2. In turn, Twist1 and Twist2 can block the transactivation activity of NF-kB in a promoter-specific matter (45).

Photos of our group throughout the years

Photo Group

From Left to Right:

Drs. Jose J. Casasnovas Nieves, Carmelo Orengo Mercado and Hector L. Franco Coriano


Photo Group

From Left to Right:

Drs. Carmelo Orengo Mercado, Carmen L. Cadilla and Ingrid Montes Rodriguez



Photo Group

From Left to Right:

Karla Claudio Campos, Dr. Ingrid Montes Rodriguez, Prof. Jessicca Y. Renta, Drs. Carmelo Orengo Mercado and Carmen L. Cadilla. This picture was taken at the Genomics core lab, where the Ion Proton Semiconductor Sequencer is located.


Photo Group

From Left to Right:

Dr. Ingrid Montes Rodriguez, Dr. Carmelo Orengo Mercado and Yacidzohara Rodriguez

Selected Publications:

Rodriguez Y, Gonzalez-Mendez RR, Cadilla CL (2016) Evolution of the Twist Subfamily Vertebrate Proteins: Discovery of a Signature Motif and Origin of the Twist1 Glycine-Rich Motifs in the Amino-Terminus Disordered Domain. PLoS One. 11(8):e0161029. PMID: 27556926

García-Crespo K, Cadilla C, Skolasky R, Meléndez LM (2010) Restricted HIV-1 replication in placental macrophages is caused by inefficient viral transcription. J Leukoc Biol. 2010 Apr;87(4):633-6. PMID: 20042472. PMCID: PMC2858303

Ramos C, Pietri R, Lorenzo W, Roman E, Granell LB, Cadilla CL, López-Garriga J (2010) Recombinant hemoglobin II from Lucina pectinata: a large-scale method for hemeprotein expression in E. coli. Protein J. 2010 Feb;29(2):143-51.PMID: 20221789. PMCID: PMC2873899.

García-Fragoso L, García-García I, Leavitt G, Renta J, Ayala MA, Cadilla CL (2010) MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers. Int J Genetics Mol Biol, 2: 43-47. PMID: 20657745 PMCID: PMC2908276

Tukel T, Sosic D, Al-Gazali LI, Erazo M, Casasnovas J, Franco HL, Richardson JA, Olson EN, Cadilla CL and Desnick RJ (2010) Homozygous Nonsense Mutations in TWIST2 Cause Setleis Syndrome. Am J Hum Genet 87: 289-296. PMID: 20691403 PMCID: PMC2917720

Torres-Serrant M, Ramirez S, Echevarría M, Cadilla CL PhD, Ramos-Valencia G and  Santiago-Borrero PJ (2010) Newborn screening for Hermansky-Pudlak Syndrome type 3 in Puerto Rico. J Pediatric Hematology/Oncology, 32: 448-453. PMID: 20562649 PMCID: PMC3640623

Franco HL, Casasnovas J, Rodríguez-Medina JR and Cadilla CL (2011) Redundant or Separate Factors? Roles of Twist1 and Twist2 as molecular switches in gene transcription. Nucleic Acids Res 39(4):1177-86. PMID: 20935057 PMCID: PMC3045590

Lojo L, Santiago-Borrero P, Rivera E, Renta J, Cadilla CL (2011) Asymptomatic Child Heterozygous for Hemoglobin S and Hemoglobin Pôrto Alegre. Pediatric Blood and Cancer, 56(3):458-9. PMID: 21225927 PMCID: PMC3664055

Franco HL, Casasnovas JJ, Leon RG, Friesel R, Ge Y, Desnick RJ, Cadilla CL (2011) Nonsense mutations of the bHLH transcription factor TWIST2 found in Setleis Syndrome patients cause dysregulation of periostin. Int J Biochem Cell Biol. 43(10):1523-31. PMID: 21801849 PMCID: PMC3163740

Mahadeo KM, Diop-Bove N, Ramirez SI, Cadilla CL, Rivera E, Martin M, Lerner NB, DiAntonio L, Duva S, Santiago-Borrero PJ, Goldman ID (2011) Prevalence of a loss-of-function mutation in the proton-coupled folate transporter gene (PCFT-SLC46A1) causing hereditary folate malabsorption in Puerto Rico. J Pediatr. 159(4):623-7.e1. PMID: 21489556  PMCID: PMC3935241

Valentin II, Vazquez J, Rivera-Miranda G, Seip RL, Velez M, Kocherla M, Bogaard K, Cruz-Gonzalez I, Cadilla CL, Renta JY, Feliu JF, Ramos AS, Alejandro-Cowan Y, Gorowski K, Ruaño G, Duconge J (2012) Prediction of warfarin dose reductions in Puerto Rican patients, based on combinatorial CYP2C9 and VKORC1 genotypes. Ann Pharmacother. 46(2):208-18. PMID: 22274142. PMCID: PMC3378722

Rodriguez-Franco EJ, Cantres-Rosario YM, Plaud-Valentin M, Romeu R, Rodríguez Y, Skolasky R, Meléndez V, Cadilla CL, Melendez LM (2012) Dysregulation of Macrophage-Secreted Cathepsin B Contributes to HIV-1-Linked Neuronal Apoptosis. PLoS One. 7(5):e36571.  PMID: 22693552. PMCID: PMC3365072

Carmona-Rivera C, D R Simeonov, N D Cardillo, WA Gahl, CL Cadilla (2013) A divalent interaction between HPS1 and HPS4 is required for the formation of the Biogenesis of Lysosome-related Organelle Complex -3 (BLOC-3). Biochimica Biophysica Acta Molecular Cell Research, 1833(3):468-78. PMID: 23103514 PMC3556189

Ramos AS, Seip RL, Rivera-Miranda G, Felici-Giovanini ME, Garcia-Berdecia R, Alejandro-Cowan Y, Kocherla M, Cruz I, Feliu JF, Cadilla CL, Renta JY, Gorowski K, Vergara C, Ruaño G, Duconge J (2012) Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients. Pharmacogenomics 13(16):1937-50. PMID: 23215886 PMC3538136

Rodríguez-Agramonte F, Izquierdo NJ, Cadilla C (2013) Ocular findings in patients with oculocutaneous albinism type Ia with G47D tyrosinase gene mutation in Puerto Rico: a case report. Bol Asoc Med P R 105(2):62-4. PMID: 23882993, PMC4042624

Orengo-Mercado C, Nieves B, López L, Vallés-Ortiz N, Renta JY, Santiago-­‐Borrero PJ, Cadilla CL and Duconge J (2013) Frequencies of functional polymorphisms in three pharmacokinetic genes of clinical interest within the admixed Puerto Rican population. J Pharmacogenom Pharmacoproteomics 4: 1. PMID: 24040574, PMC3769800

Duconge J, Cadilla CL (2013) CYP2D6’s functional status associated with the length of hospitalization stay in psychiatric patients: a twist in the tale or evidence that matters? Biomark Med. 7(6):913-4. PMID: 24266824, PMC4109677.

Jardón J, Izquierdo NJ, Renta JY, García-Rodríguez O, Cadilla CL (2015) Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3) Ophthalmic Genet. 21:1-6. PMID: 24766090. PMC4232478.

Valentín II, Rivera G, Nieves-Plaza M, Cruz I, Renta JY, Cadilla CL, Feliu JF, Seip RL, Ruaño G, Duconge J (2014) Pharmacogenetic association study of warfarin safety endpoints in Puerto Ricans. P R Health Sci J. 33(3):97-104. PMID: 25244877, PMC4196861. PMCID: PMC4196861.

Rosti RO, Uyguner ZO, Nazarenko I, Bekerecioglu M, Cadilla CL, Ozgur H, Lee BH, Aggarwal AK, Pehlivan S, Desnick RJ (2015) Setleis syndrome: clinical, molecular and structural studies of the first TWIST2 missense mutation. Clin Genet. 88(5):489-93. PMID: 25410422. PMCID: PMC4769376.

Claudio-Campos K, Duconge J, Cadilla CL, Ruaño G (2014) Pharmacogenetics of drug-metabolizing enzymes in US Hispanics. Drug Metabol Drug Interact. 30(2):87-105 PMID: 25431893 [PubMed – in process] PMC4447600. PMCID: PMC4447600.

Claudio-Campos K, Orengo-Mercado C, Renta JY, Peguero M, García R, Hernández G, Corey S, Cadilla CL, Duconge J (2015) Pharmacogenetics of healthy volunteers in Puerto Rico. Drug Metabol Personal Ther. 2015 Dec 1;30(4):239-49. PMID: 26501165. PMCID: PMC4768757

Díaz-Ayala R, Moya-Rodríguez A, Pietri R, Cadilla CL, López-Garriga J (2015) Molecular Cloning and Characterization of a (Lys)6-Tagged Sulfide-Reactive Hemoglobin I from Lucina pectinata. Mol Biotechnol. 2015 Oct 19. [Epub ahead of print]. PMID: 26482241

Duconge J, Cadilla CL, Seip RL, Ruaño G (2015) Why admixture matters in genetically-guided therapy: missed targets in the COAG and EU-PACT trials. P R Health Sci J. 34(3):175-7. PMID: 26454897. PMCID: PMC4770896.

Claudio-Campos K, Duconge J, Cadilla CL, Ruaño G (2105) Pharmacogenetics of drug-metabolizing enzymes in US Hispanics. Drug Metabol Personal Ther. 30(2):87-105. PMID: 25431893.

Suárez E, González L, Pérez-Mitchell C, Ortiz AP, Ramírez-Sola M, Acosta J, Bernabe-Dones RD, González-Aquino C, Montes-Rodríguez I, Cadilla CL (2016) Pathway Analysis using Gene-expression Profiles of HPV-positive and HPV-negative Oropharyngeal Cancer Patients in a Hispanic Population: Methodological Procedures. P R Health Sci J. 35(1):3-8. PMID: 26932277

Montes-Rodríguez IM, Rivera LE, López-Garriga J, Cadilla CL (2016) Characterization and Expression of the Lucina pectinata Oxygen and Sulfide Binding Hemoglobin Genes. PLoS One. 11(1):e0147977. PMID: 26824233. PMCID: PMC4732748.

Duconge J, Ramos AS, Claudio-Campos K, Rivera-Miranda G, Bermúdez-Bosch L, Renta JY, Cadilla CL, Cruz I, Feliu JF, Vergara C, Ruaño G A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics (2016) PLoS One. 11(1):e0145480. PMID: 26745506. PMCID: PMC4706412.