Carrie Welch, PhD

  • Assistant Professor of Medical Sciences (in Pediatrics) at the Columbia University Medical Center
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Overview

Dr Welch is a basic science researcher with a focus on rare disease as well as complex trait genetics. She received her PhD from UCLA (mentor: Aldons J Lusis, PhD) and completed her post-doctoral work at Columbia University (mentor: Alan R. Tall, MD). Her early work focused on identifying the genetic architecture of atherosclerosis and disease gene mapping utilizing mouse models of atherosclerosis. She currently works with Dr. Wendy Chung to identify rare variants underlying pulmonary arterial hypertension and other rare human diseases.

Academic Appointments

  • Assistant Professor of Medical Sciences (in Pediatrics) at the Columbia University Medical Center

Credentials & Experience

Education & Training

  • MPH, 1990 Nutrition and Food Sciences, UCLA
  • PhD, 1996 Cellular & Molecular Pathology, UCLA School of Medicine

Committees, Societies, Councils

American Heart Association since 2014

American Society of Human Genetics since 2017

Institute Animal Care and Use Committee, faculty member since 2014

Research

We are using a mouse genetics approach to identify new genes underlying susceptibility to atherosclerosis and thrombosis.

Selected Publications

Welch, C.L., Xia, Y.R., Shechter, I., Farese, R., Mehrabian, M., Mehdizadeh, S., Warden, C.H., & Lusis, A.J. (1996). Genetic regulation of cholesterol homeostasis: chromosomal organization of candidate genes. Journal of Lipid Research, 37(7), 1406-1421.

Welch, C.L., Xia, Y.R., Gu, L.J., Machleder, D., Mehrabian, M., Wen, P.Z., Webb, N., deVilliers, W.J.S., van der Westhuyzen, D., & Lusis, A.J. (1997). Srb1 maps to mouse Chromosome 5 in a region harboring putative QTLs for plasma lipoprotein levels. Mammalian Genome, 8(12), 942-944.

Meiner, V.L., Welch, C.L., Cases, S., Myers, H.M., Sande, E., Lusis, A.J., & Farese, R.V. (1997). Adrenocortical lipid depletion gene (ald) in AKR mice is associated with an acyl CoA:cholesterol acyltransferase (ACAT) mutation. Journal of Biological Chemistry, 273(2), 1064-1069.

Cases, S., Smith, S.J., Zheng, Y.W., Myers, H.M., Lear, S.R., Sande, E., Novak, S., Collins, C., Welch, C.B., Lusis, A.J., Erickson, S.K., & Farese, R.V. (1998). Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proceedings of the National Academy of Sciences U.S.A., 95(22), 13018-13023.

Cases, S., Novak, S., Zheng, Y.W., Myers, H.M., Lear, S.R., Sande, E., Welch, C.B., Lusis, A.J., Spencer, T.A., Krause, B.R., Erickson, S.K., Farese, R.V. (1998). ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. Journal of Biological Chemistry, 273(41), 26755-26764.

Arai, T., Wang, N., Bezouevski, M., Welch, C. & Tall, A.R. (1999). Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. Journal of Biological Chemistry, 274, 2366-2371.

Klingenspor, M., Xu, P., Cohen, R.D., Welch, C., & Reue, K. (1999). Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics. Journal of Biological Chemistry, 274(33), 23078-23084.

Welch, C.L., Bretschger, S., Latib, N., Bezouevski, M., Guo, Y., Pleskac, N., Liang, C.P., Barlow, C., Dansky, H., Breslow, J.L., & Tall, A.R. (2001). Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knock-out mouse model. Proceedings of the National Academy of Sciences U.S.A., 98, 7946-7951.

Welch, C.L., Bretschger, S., Wen, P.Z., Mehrabian, M., Latib, N., Fruchart-Najib, J., Fruchart, J.C., Myrick, C., & Lusis, A.J. (2004). Novel QTLs for HDL-C levels identified by controlling for the major gene effect of Apoa2: confirmation of a chromosome 6 locus in a congenic strain. Physiological Genomics, 17(1), 48-59.

Seidelmann, S.B., De Luca, C., Leibel, R.L., Breslow, J.L., Tall, A.R., & Welch, C.L. (2005). Quantitative trait locus mapping of genetic modifiers of metabolic syndrome and atherosclerosis in LDL receptor deficient mice: identification of a locus for metabolic syndrome and increased atherosclerosis on chromosome 4. Arteriosclerosis, Thrombosis and Vascular Biology, 25, 204-210.

Ranalletta, M., Wang, N., Han, S., Yvan-Charvet, L., Welch, C., & Tall, A.R. (2006). Decreased atherosclerosis in LDL receptor knock-out mice transplanted with ABCG1 deficient bone marrow: compensatory induction of Abca1 and apoE secretion by Abcg1-/- macrophages. Arteriosclerosis, Thrombosis and Vascular Biology, 26, 2308-2315.

Welch, C.L., Sun, Y., Arey, B., Lemaitre, V., Sharma, N., Ishibashi, M., Sayers, S., Li, R., Gorelik, A., Pleskac, N., Collins-Fletcher, K., Yasuda, Y., Bromme, D., D'Armiento, J.M., Ogletree, M.L., & Tall, A.R. (2007). Spontaneous atherothrombosis and medial degradation in Apoe-/-, Npc1-/- mice. Circulation, 116, 2444-2452.

Yvan-Charvet, L., Ranalletta, M., Wang, N., Han, S., Terasaka, N., Li, R., Welch, C., & Tall, A.R. (2007). Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. Journal of Clinical Investigation, 117(12), 3900-3908.

Yvan-Charvet, L., Welch, C., Pagler, T., Ranaletta, M., Lamkanfi, M., Han, S., Ishibashi, M., Li, R., Wang, N., & Tall, A.R. (2008). Increased inflammatory gene expression in ABC transporter deficient macrophages: free cholesterol accumulation, increased signaling via Toll-like receptors and neutrophil infiltration of atherosclerotic lesions. Circulation, 118, 1837-1847.

Seidelmann, S.B., Kuo, C., Pleskac, N., Molina, J., Sayers, S., Li, R., Zhou, J., Johnson, P., Braun, K., Chan, C., Teupser, D., Breslow, J.L., Wight, T.N., Tall, A.R., & Welch, C.L. (2008). Athsq1 is an atherosclerosis modifier locus with dramatic effects on lesion area and prominent accumulation of versican. Arteriosclerosis, Thrombosis and Vascular Biology, 28, 2180-2186.

Terasaka, N., Yu, S., Yvan-Charvet, L., Wang, N., Mzhavia, N., Langlois, R., Pagler, T., Li, R., Welch, C.L., Goldberg, I.J., & Tall, A.R. (2008). ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet. Journal of Clinical Investigation, 118, 3701-3713.

Sun, Y., Ishibashi, M., Seimon, T., Lee, M., Sharma, S.M., Fitzgerald, K.A., Samokhin, A.O., Wang, Y., Sayers, S., Aikawa, M., Jerome, W.G., Ostrowski, M.C., Bromme, D., Libby, P., Tabas, I.A., Welch, C.L., & Tall, A.R. (2009). Free cholesterol accumulation in macrophage membranes activates toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K. Circulation Research, 104, 455-465.

Yvan-Charvet, L, Pagler, T.A., Seimon, T.A., Thorp, E., Welch, C.L., Wiztum, J.L., Tabas, I., & Tall, A.R. (2010). ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis. Circulation Research, 106(12), 1861-1869.

Kuo, C.L., Murphy, A.J., Sayers, S., Li, R., Yvan-Charvet, L., Davis, J.Z., Krishnamurthy, J., Liu, Y., Puig, O., Sharpless, N.E., Tall, A.R. & Welch, C.L. (2011). Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation. Arteriosclerosis Thrombosis & Vascular Biology, 31(11), 2483-2492.

Qiang, L., Tsuchiya, K., Kim-Muller, J-A., Lin, H.V., Welch, C. & Accili, D. (2012). Increased atherosclerosis and endothelial dysfunction in mice bearing constitutively-deacetylated alleles of Foxo1 gene. Journal of Biological Chemistry, 287(17), 13944-13951.

Murphy, A.J., Bijl, N., Yvan-Charvet, L., Welch, C.B., Bhagwat, N., Reheman, A., Wang, Y., Shaw, J.A., Levine, R.L., Ni, H., Tall, A.R. & Wang, N. (2013). Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nature Medicine, 19(5): 586-594.

Wang, W., Oh, S., Koester, M., Abramowicz, S., Wang, N., Tall, A.R. and Welch, C.L. 2016. Enhanced megakaryopoiesis and platelet activity in hypercholesterolemic Cdkn2a-deficient mice. Circulation: Cardiovascular Genetics, 9(3): 213-222.

Hsieh, J., Koseki, M., Molusky, M., Yakushiji, E., Ichi, I., Westerterp, Iqbal, J., Chan, R.B., M., Abramowicz, S., Tascau, L., Takiguchi, S., Yamashita, S., Welch, C., Di Paolo, G., Hussain, M.M., Lefkowitch, J.H., Rader, D.J., and Tall, A.R. (2016). TTC39B deficiency stabilizes LXR reducing both atherosclerosis and steatohepatitis. Nature, 535(7611): 303-307.

Zhu*, N., Gonzaga-Jauregui*, C., Welch*, C., Ma, L., Qi, H., King, A.K., Krishnan, U., Rosenzweig, E.B., Ivy, D., Austin, E.D., Hamid, R., Nichols, W.C., Pauciulo, M.W., Lutz, K.A., Sawle, A., Reid, J.G., Overton, J.D., Baras, A., Dewey, F., Shen, Y., and Chung, W.K. (2018). Exome sequencing in children with pulmonary arterial hypertension demonstrates differences compared to adults. Circulation: Genomics and Precision Medicine, 11(4): e001887.

Zhu*, N., Welch*, C., Wang, J. Allen, P.M., Gonzaga-Jauregui, C., Ma, L., King, A.K., Krishnan, U., Rosenzweig, E.B., Ivy, D., Austin, E.D., Hamid, R., Nichols, W.C., Pauciulo, M.W., Lutz, K.A., Reid, J.G., Overton, J.D., Baras, A., Dewey, F., Shen, Y., and Chung, W.K. (2018). Rare variants associated with pulmonary arterial hypertension associated with congenital heart disease. Genomic Medicine, 10(1): 56-66.

Zhu*, N., Pauciulo*, M.W., Welch*, C.L., Lutz, K.A., Coleman, A.W., Wang, J., Gonzage-Jauregui, C., Grimes, J.M., PAH Biobank, Shen, Y., Chung, W.K. and Nichols, W.C. (2019). Novel risk genes and mechanisms implicated by exome sequencing of 2,572 individuals with pulmonary arterial hypertension. Nature Communications, submitted.

Potus*, F., Pauciulo*, M.W., Cook, E.K., Zhu, N., Hsieh, A., Welch, C.L., Shen, Y., Lian, T., Lima, P., Mewburn, J., D'Arsigny, C.L., Lutz, K.A., Coleman, A.W., Damico, R., Hassoun, P.W., Nichols, W.C., Chung, W.K., Rauh, M.J. and Archer, S.L. (2019). Novel mutations and decreased expression of epigenetic regulator TET2 in pulmonary arterial hypertension. The Lancet, submitted.